tag:theconversation.com,2011:/uk/topics/immune-system-901/articlesImmune system – The Conversation2024-03-27T16:02:40Ztag:theconversation.com,2011:article/2257002024-03-27T16:02:40Z2024-03-27T16:02:40ZHazardous mould contaminates many food staples – what you should know about mycotoxins<p><em>Mycotoxins are substances produced by mould that poison food. They are <a href="https://academic.oup.com/carcin/article/31/1/71/2392129">harmful</a> to humans and animals when consumed. According to the Food and Agricultural Organisation (FAO), about 25% of the world’s agricultural harvests are <a href="https://pureadmin.qub.ac.uk/ws/files/185127566/Worldwide_contamination_of_food_crops_with_mycotoxins_Validity_of_the_widely_cited_FAO_estimate_of_25.pdf">contaminated</a> by mycotoxins. Though reliable data is lacking, mycotoxin contamination is <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4108760/">widespread in Africa</a>. It often takes the form of aflatoxin in cereal crops and has led to <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6354945/#:%7E:text=They%20have%20the%20ability%20to,of%20humans%20annually%20(15).">health issues</a> such as chronic gastritis, diarrhoea, kidney problems and <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3699030/">liver cancer</a>. Biologist Oluwadara Pelumi Omotayo <a href="https://www.sciencedirect.com/science/article/pii/S2214750018307315">studied</a> how mycotoxins contaminate ginger in South Africa. We asked her to explain what they are and how to avoid the danger.</em></p>
<hr>
<h2>What are mycotoxins?</h2>
<p>Mycotoxins are hazardous substances produced by certain microorganisms called toxigenic fungi (<a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4108760/">moulds</a>). </p>
<p>One mould species may produce more than one type of mycotoxin, and a single mycotoxin may be produced by several mould species. Mycotoxins are ubiquitous. They can be found indoors and outdoors, thriving in warm and highly humid areas. They are usually toxic to living things. </p>
<p>Contamination can lead to variety of illnesses, and even death. They can cause <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4108760/">cancer</a>, <a href="https://www.sciencedirect.com/science/article/abs/pii/B9780323870313000305">hepatic diseases</a>, deterioration of the <a href="https://journals.sagepub.com/doi/abs/10.1191/0960327103ht328oa">kidneys</a>, <a href="https://journals.sagepub.com/doi/abs/10.1191/0960327103ht328oa">nephropathy</a>, and <a href="https://core.ac.uk/download/481757543.pdf">alimentary toxic aleukia</a>, a potentially fatal illness marked by nausea, vomiting, diarrhoea and skin inflammation. They can also impair an animal’s immune system, decrease milk production, cause stunted growth and weight loss, and induce gastroenteritis. </p>
<p>Mycotoxins have been reported to be responsible for numerous human deaths. For example, in 2004, Kenya <a href="https://www.devex.com/news/kenyans-love-maize-but-aflatoxins-are-making-it-dangerous-96279">recorded</a> an outbreak of aflatoxin poisoning which led to the death of about 125 people.</p>
<p>Mycotoxins drastically suppress the immune system. And a single mycotoxin, even in minute quantities, can result in acute poisoning in humans and animals.</p>
<p>Over 300 types of mycotoxins have been identified so far, including the notable aflatoxin and other types like ochratoxin and fumonisin, which often contaminate grains like maize. </p>
<h2>How do humans come in contact with mycotoxin?</h2>
<p>People can be exposed to mycotoxins through eating contaminated food and through contact and absorption through the skin. Exposure can also happen through inhalation of polluted air, as they can be present in airborne particles such as fungal spores.</p>
<p>Human exposure to mycotoxins can come from plant-based food and from the carry-over of mycotoxins and their metabolites in animal products such as meats.</p>
<p>Food items that can be tainted include spices, grains (such as maize, rice and sorghum), nuts, fruits (dry or fresh), coffee beans, cocoa seeds, vegetables and rhizomes like ginger.</p>
<h2>Why should we be concerned about mycotoxins?</h2>
<p>Mycotoxin contamination is widespread, especially in African countries. The toxins exist even in medicinal plants and herbs. This was confirmed by our <a href="https://www.sciencedirect.com/science/article/pii/S2214750018307315">study</a>, which investigated the presence of mycotoxin in ginger. </p>
<p>Ginger has been used since antiquity for the treatment of various ailments such as colds, migraines and gastrointestinal tract disorders. However, like other spices and herbs, it has been reported to contain mycotoxins. Ginger has been found to contain aflatoxin and ochratoxin A (which is known to be teratogenic: capable of causing developmental abnormalities in unborn foetuses). </p>
<p>From our study, aflatoxins B1, B2, G1 and G2 and ochratoxin A were found in ginger collected from the North-West province of South Africa in summer and winter. Though at varying concentrations, the highest concentration was observed in summer. This indicates that there’s no period when crops and plants, including ginger, would necessarily be completely free from mycotoxins.</p>
<h2>How do farmers and consumers know that a crop has been contaminated?</h2>
<p>Mycotoxins are not visible to the naked eye. The invasion of crops and foods by moulds is an indication that they are potentially contaminated with mycotoxins. </p>
<p>Farmers and consumers should inspect food crops for evidence of moulds, and discard crops and food that have mould growth. </p>
<h2>What can be done to prevent mycotoxin contamination?</h2>
<p>To minimise the risk of mycotoxin exposure and contamination, we recommend action before and after harvest and storage.</p>
<ul>
<li><p>Prevent mycotoxin/fungi invasion while the crops are still in the field. This can be achieved by cultivating and harvesting at the appropriate time. Adopt techniques that reduce stress in plants, such as ensuring they get enough water and are well spaced. They also need adequate sunlight and should be cultivated on suitable soil. It is also important to avoid using agricultural residues as compost as they can produce toxigenic fungi and mycotoxins when decaying.</p></li>
<li><p>After harvest, reduce fungal contamination and mycotoxin production in foods during storage, handling, processing and transport. Facilities should be monitored and kept at temperatures that discourage mould growth. Crops with moulds should be sorted and removed before storage. Storage facilities must be aerated and dry. Reducing moisture content in crops before storage is important to prevent mould.</p></li>
<li><p>Avoid damage to grains before storing as damaged grain is more susceptible to mould growth and mycotoxin contamination.</p></li>
<li><p>Don’t store food too long before consumption. It is important to follow recommended guidelines for safely storing <a href="https://www.foodsafety.gov/food-safety-charts/cold-food-storage-charts">cooked and raw food</a> in the <a href="https://www.foodsafety.gov/food-safety-charts/food-safety-during-power-outage">refrigerator</a>, <a href="https://www.agric.wa.gov.au/fruit/storage-fresh-fruit-and-vegetables?nopaging=1">fruits and vegetables</a>, <a href="https://wholegrainscouncil.org/recipes/cooking-whole-grains/storing-whole-grains">grains</a>, <a href="https://wildlyorganic.com/blogs/recipes/how-long-do-nuts-last-tips-for-storing-nuts-and-seeds">nuts and seeds</a>, and spices such as <a href="https://eatbydate.com/other/spice-menu/how-long-does-ginger-last-shelf-life/">ginger</a>. </p></li>
<li><p>Inspect and discard foods contaminated by moulds. </p></li>
<li><p>Ensure contaminated foods are not sold to consumers.</p></li>
<li><p>Improve awareness about mycotoxin contamination.</p></li>
</ul><img src="https://counter.theconversation.com/content/225700/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Oluwadara Pelumi Omotayo does not work for, consult, own shares in or receive funding from any company or organisation that would benefit from this article, and has disclosed no relevant affiliations beyond their academic appointment.</span></em></p>Mycotoxins contamination causes health issues. Paying attention to storage of agricultural produce can save many lives.Oluwadara Pelumi Omotayo, Postdoctoral Research Fellow, North-West UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/2235232024-03-08T13:37:11Z2024-03-08T13:37:11ZImmune cells can adapt to invading pathogens, deciding whether to fight now or prepare for the next battle<figure><img src="https://images.theconversation.com/files/579022/original/file-20240229-16-4ad8vr.jpg?ixlib=rb-1.1.0&rect=0%2C0%2C2000%2C1500&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Understanding the flexibility of T cell memory can lead to improved vaccines and immunotherapies.</span> <span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/illustration/maturing-t-lymphocyte-illustration-royalty-free-illustration/1489195717">Juan Gaertner/Science Photo Library via Getty Images</a></span></figcaption></figure><p>How does your immune system decide between fighting invading pathogens now or preparing to fight them in the future? Turns out, it can <a href="https://doi.org/10.1016/j.immuni.2023.12.006">change its mind</a>.</p>
<p>Every person has <a href="https://doi.org/10.1073/pnas.1409155111">10 million to 100 million unique T cells</a> that have a critical job in the immune system: patrolling the body for invading pathogens or cancerous cells to eliminate. Each of these T cells has a unique receptor that allows it to recognize foreign proteins on the surface of infected or cancerous cells. When the right T cell encounters the right protein, it rapidly forms many copies of itself to destroy the offending pathogen. </p>
<p>Importantly, this process of proliferation gives rise to both short-lived effector T cells that shut down the immediate pathogen attack and long-lived memory T cells that provide protection against future attacks. But how do T cells decide whether to form cells that kill pathogens now or protect against future infections?</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/580789/original/file-20240308-16-w72oqc.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="Diagram of cytotoxic T cell killing a target cell" src="https://images.theconversation.com/files/580789/original/file-20240308-16-w72oqc.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/580789/original/file-20240308-16-w72oqc.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=418&fit=crop&dpr=1 600w, https://images.theconversation.com/files/580789/original/file-20240308-16-w72oqc.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=418&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/580789/original/file-20240308-16-w72oqc.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=418&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/580789/original/file-20240308-16-w72oqc.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=526&fit=crop&dpr=1 754w, https://images.theconversation.com/files/580789/original/file-20240308-16-w72oqc.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=526&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/580789/original/file-20240308-16-w72oqc.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=526&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Cytotoxic T cells bind to foreign proteins on infected or cancerous cells and subsequently destroy those target cells by releasing molecules like granzyme and perforin.</span>
<span class="attribution"><a class="source" href="https://pressbooks.ccconline.org/bio106/chapter/lymphatic-levels-of-organization/">Anatomy & Physiology/SBCCOE</a>, <a class="license" href="http://creativecommons.org/licenses/by-nc-sa/4.0/">CC BY-NC-SA</a></span>
</figcaption>
</figure>
<p><a href="https://www.researchgate.net/scientific-contributions/Kathleen-Abadie-2232092055">We are</a> <a href="https://www.researchgate.net/scientific-contributions/Elisa-Clark-2148857839">a team</a> <a href="https://scholar.google.com/citations?user=ckyY7T8AAAAJ&hl=en">of bioengineers</a> studying how immune cells mature. In our <a href="https://doi.org/10.1016/j.immuni.2023.12.006">recently published research</a>, we found that having multiple pathways to decide whether to kill pathogens now or prepare for future invaders boosts the immune system’s ability to effectively respond to different types of challenges.</p>
<h2>Fight or remember?</h2>
<p>To understand when and how T cells decide to become effector cells that kill pathogens or memory cells that prepare for future infections, we <a href="https://doi.org/10.1016/j.immuni.2023.12.006">took movies of T cells dividing</a> in response to a stimulus mimicking an encounter with a pathogen. </p>
<p>Specifically, we tracked the activity of a gene called T cell factor 1, or TCF1. This gene is essential for the longevity of memory cells. We found that stochastic, or probabilistic, silencing of the TCF1 gene when cells confront invading pathogens and inflammation <a href="https://doi.org/10.1016/j.immuni.2023.12.006">drives an early decision</a> between whether T cells become effector or memory cells. Exposure to higher levels of pathogens or inflammation increases the probability of forming effector cells.</p>
<p>Surprisingly, though, we found that some effector cells that had turned off TCF1 early on were able to <a href="https://doi.org/10.1016/j.immuni.2023.12.006">turn it back on</a> after clearing the pathogen, later becoming memory cells. </p>
<p>Through mathematical modeling, we determined that this flexibility in decision making among memory T cells is critical to generating the right number of cells that respond immediately and cells that prepare for the future, appropriate to the severity of the infection. </p>
<h2>Understanding immune memory</h2>
<p>The proper formation of persistent, long-lived T cell memory is critical to a person’s ability to fend off diseases ranging from the common cold to COVID-19 to cancer.</p>
<p>From a <a href="https://doi.org/10.1016/0377-2217(93)E0210-O">social and cognitive science perspective</a>, flexibility allows people to adapt and respond optimally to uncertain and dynamic environments. Similarly, for immune cells responding to a pathogen, flexibility in decision making around whether to become memory cells may enable greater responsiveness to an evolving immune challenge.</p>
<p>Memory cells can be <a href="https://doi.org/10.1016/j.immuni.2018.02.010">subclassified into different types</a> with distinct features and roles in protective immunity. It’s possible that the pathway where memory cells diverge from effector cells early on and the pathway where memory cells form from effector cells later on give rise to particular subtypes of memory cells. </p>
<p>Our study focuses on T cell memory in the context of acute infections the immune system can successfully clear in days, such as cold, the flu or food poisoning. In contrast, chronic conditions such as HIV and cancer require persistent immune responses; long-lived, memory-like cells are critical for this persistence. Our team is investigating whether flexible memory decision making also applies to chronic conditions and whether we can leverage that flexibility to improve cancer immunotherapy.</p>
<p>Resolving uncertainty surrounding how and when memory cells form could help improve vaccine design and therapies that boost the immune system’s ability to provide long-term protection against diverse infectious diseases.</p>
<p><em>This article was updated to replace a figure of T cell differentiation with cytotoxic T cell activity.</em></p><img src="https://counter.theconversation.com/content/223523/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Kathleen Abadie was funded by a NSF (National Science Foundation) Graduate Research Fellowships. She performed this research in affiliation with the University of Washington Department of Bioengineering. </span></em></p><p class="fine-print"><em><span>Elisa Clark performed her research in affiliation with the University of Washington (UW) Department of Bioengineering and was funded by a National Science Foundation Graduate Research Fellowship (NSF-GRFP) and by a predoctoral fellowship through the UW Institute for Stem Cell and Regenerative Medicine (ISCRM). </span></em></p><p class="fine-print"><em><span>Hao Yuan Kueh receives funding from the National Institutes of Health.</span></em></p>When faced with a threat, T cells have the decision-making flexibility to both clear out the pathogen now and ready themselves for a future encounter.Kathleen Abadie, Ph.D. Candidate in Bioengineering, University of WashingtonElisa Clark, Ph.D. Candidate in Bioengineering, University of WashingtonHao Yuan Kueh, Associate Professor of Bioengineering, University of WashingtonLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/2213842024-01-21T12:59:06Z2024-01-21T12:59:06ZDietary fibre affects more than your colon: How the immune system, brain and overall health benefit too<figure><img src="https://images.theconversation.com/files/570412/original/file-20240119-19-bkynf2.jpg?ixlib=rb-1.1.0&rect=66%2C6%2C3923%2C2249&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Most people only consume about half of the recommended amount of dietary fibre, and it can negatively affect overall health.</span> <span class="attribution"><span class="source">(Shutterstock)</span></span></figcaption></figure><iframe style="width: 100%; height: 100px; border: none; position: relative; z-index: 1;" allowtransparency="" allow="clipboard-read; clipboard-write" src="https://narrations.ad-auris.com/widget/the-conversation-canada/dietary-fibre-affects-more-than-your-colon-how-the-immune-system-brain-and-overall-health-benefit-too" width="100%" height="400"></iframe>
<p>There’s no shortage of advice about what to eat, including hype about the latest <a href="https://www.hsph.harvard.edu/nutritionsource/superfoods/">superfoods</a> that will help you <a href="https://www.npr.org/sections/thesalt/2015/04/11/398325030/eating-to-break-100-longevity-diet-tips-from-the-blue-zones">live to 100</a>, or about the newest <a href="https://food-guide.canada.ca/en/tips-for-healthy-eating/diets-food-trends/#section-2">restrictive diets</a> that claim to help you lose weight and look beautiful. As a researcher from the <a href="https://farncombe.mcmaster.ca/">Farncombe Family Digestive Health Research Institute</a>, I’m well aware that there is no universal “healthy diet” that will work for everyone. </p>
<p>However, most professionals would agree that a diet should be well balanced between the food groups, and it’s better to include more things like vegetables and <a href="https://doi.org/10.3390%2Fnu11081806">fermented foods</a> in your diet than restrict yourself unnecessarily. Eating foods that promote gut health improves your overall health too.</p>
<h2>Why is everyone so concerned about fibre?</h2>
<p>The importance of fibre has been known for decades. The late great surgeon and fibre researcher <a href="https://doi.org/10.1017/S0954422417000117">Denis Burkitt</a> once said, “If you pass small stools, you have to have large hospitals.” But dietary fibre does more than just help move your bowels. Fibre can be considered a <a href="https://www.mayoclinic.org/healthy-lifestyle/nutrition-and-healthy-eating/expert-answers/probiotics/faq-20058065">prebiotic nutrient</a>. </p>
<p>Prebiotics aren’t actively digested and absorbed, rather they are selectively used to promote the growth of a beneficial species of microbes in our gut. <a href="https://doi.org/10.3390%2Ffoods8030092">These microbes then help digest foods</a> for us so we can obtain more nutrients, promote gut barrier integrity and prevent the growth of harmful bacteria. </p>
<figure class="align-center ">
<img alt="High-fibre foods against the outline of intestines" src="https://images.theconversation.com/files/570413/original/file-20240119-17-wpd6x9.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/570413/original/file-20240119-17-wpd6x9.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/570413/original/file-20240119-17-wpd6x9.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/570413/original/file-20240119-17-wpd6x9.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/570413/original/file-20240119-17-wpd6x9.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/570413/original/file-20240119-17-wpd6x9.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/570413/original/file-20240119-17-wpd6x9.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=503&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">Prebiotics aren’t actively digested and absorbed, rather they are selectively used to promote the growth of a beneficial species of microbes in our gut.</span>
<span class="attribution"><span class="source">(Shutterstock)</span></span>
</figcaption>
</figure>
<p>Fibres can also have microbe-independent effects on our immune system when they <a href="https://doi.org/10.1111/bph.14871">interact directly with receptors expressed by our cells</a>. These beneficial effects may even help teach the immune system to be more tolerant and reduce inflammation.</p>
<h2>Getting enough dietary fibre?</h2>
<p>Probably not. The so-called <a href="https://doi.org/10.3390%2Fnu15122749">western diet</a> is low in fibre and filled with ultra-processed foods. The <a href="https://www.canada.ca/en/health-canada/services/nutrients/fibre.html">recommendation for daily fibre</a> is between <a href="https://doi.org/10.1038/s41575-020-00375-4">25-38 grams depending on factors like age, sex and activity level</a>. Most people consume about half of the recommendation, and it can negatively affect overall health. </p>
<p>Good sources of dietary fibre include whole grains, fruits and vegetables, beans and legumes, and nuts and seeds. There is a lot of emphasis on soluble fibres and less on insoluble fibres, but in reality, most foods will contain a mixture of both, and they each <a href="https://www.healthline.com/health/soluble-vs-insoluble-fiber%23risks">have their merits</a>. </p>
<p>High fibre snacks are also gaining popularity. With an estimated global value of US$7 billion in 2022, the <a href="https://www.precedenceresearch.com/prebiotic-ingredients-market#:%7E:text=The%2520global%2520prebiotic%2520ingredients%2520market,13.25%2525%2520from%25202022%2520to%25202030">value of the prebiotic ingredient market</a> is expected to triple by 2032.</p>
<h2>The benefits of dietary fibre</h2>
<figure class="align-right ">
<img alt="Diagram of a human with arrows linking brain and intestines" src="https://images.theconversation.com/files/570414/original/file-20240119-17-fwfmrl.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/570414/original/file-20240119-17-fwfmrl.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=600&fit=crop&dpr=1 600w, https://images.theconversation.com/files/570414/original/file-20240119-17-fwfmrl.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=600&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/570414/original/file-20240119-17-fwfmrl.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=600&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/570414/original/file-20240119-17-fwfmrl.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=754&fit=crop&dpr=1 754w, https://images.theconversation.com/files/570414/original/file-20240119-17-fwfmrl.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=754&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/570414/original/file-20240119-17-fwfmrl.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=754&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">Fibre is associated with overall health and brain health through the gut-brain axis.</span>
<span class="attribution"><span class="source">(Shutterstock)</span></span>
</figcaption>
</figure>
<p>There’s plenty of evidence supporting the benefits of dietary fibre. Fibre isn’t just associated with colon health; it’s associated with overall health and brain health through the <a href="https://my.clevelandclinic.org/health/body/the-gut-brain-connection">gut-brain axis</a>. Diets low in fibre have been associated with gastrointestinal disorders such as irritable bowel syndrome or inflammatory bowel disease. </p>
<p>On the other hand, consuming adequate fibre also <a href="https://doi.org/10.1038/s41575-020-00375-4">reduces the risk and mortality associated with cardiovascular diseases and obesity</a>. There are studies that show <a href="https://doi.org/10.3390/nu13072159">improvements of cognitive function with certain types of fibre</a>. </p>
<p>There are some gastrointestinal diseases, like Celiac disease, which are not typically associated with the benefits of dietary fibre. However, <a href="https://doi.org/10.1038/s41575-020-00375-4">there isn’t a consensus</a> to the specific type of fibre and dose that would be beneficial in treating most diseases.</p>
<h2>Not all fibre is good fibre</h2>
<p>Shockingly, not all fibre is good for you. Fibre is used as an umbrella term for indigestible plant polysaccharides, so there are many different types with varying fermentability, solubility and viscosity in the gut. </p>
<p>To make things more complex, <a href="https://doi.org/10.3389/fped.2020.620189">the source matters too</a>. Fibre from one plant isn’t the same as fibre from another plant. Additionally, the old proverb, “too much good is not good” rings true, where overconsumption of fibre supplements can cause symptoms such as constipation, bloating and gas. This is partly due to the differences in gut microbiomes that affect the ability to metabolize fibre to produce beneficial molecules like short-chain fatty acids. </p>
<p>In some cases, such as inflammatory bowel disease patients, lack of microbes with the capacity to digest fibre may allow intact fibres to <a href="https://doi.org/10.1053/j.gastro.2022.09.034">interact with intestinal cells directly and exert pro-inflammatory effects</a>. Recent evidence has even shown that excessively high consumption of soluble fibres, such as inulin, a common supplement, <a href="https://doi.org/10.1053/j.gastro.2023.10.012">can increase the risk of colon cancer development in an experimental animal model</a>.</p>
<h2>Part of a healthy diet</h2>
<p>Dietary fibre is an important part of a healthy diet that can promote both gut and overall health. Fibre helps you feel more satisfied after meals and helps to regulate your blood sugar and cholesterol. Do your best to consume fibre as part of your diet, and when needed, take only the dose of supplements as recommended. </p>
<p>Prebiotics promote the growth of gut microbes that can affect gut health and immunity in the context of many different diseases, although not all fibres are created equal. While fibre won’t cure illness, diet is a great addition to medicines and treatment strategies that can improve their efficacy.</p><img src="https://counter.theconversation.com/content/221384/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Mark Wulczynski does not work for, consult, own shares in or receive funding from any company or organisation that would benefit from this article, and has disclosed no relevant affiliations beyond their academic appointment.</span></em></p>Fibre isn’t just associated with colon health; it’s associated with overall health and brain health through the gut-brain axis. But not all fibres are created equal.Mark Wulczynski, Medical Sciences PhD Candidate, McMaster UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/2199912024-01-15T17:52:20Z2024-01-15T17:52:20ZWhy you may feel depressed and anxious when you’re ill – and how to cope with it<figure><img src="https://images.theconversation.com/files/569256/original/file-20240115-15-sbj0xe.jpg?ixlib=rb-1.1.0&rect=45%2C91%2C7551%2C5500&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">
</span> <span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/sick-black-man-530798209">kurhan/Shutterstock</a></span></figcaption></figure><p>Winter illnesses are all around us at the moment – from the common cold, COVID-19 and flu to strep throat and stomach bugs. All have one thing in common: they can make you feel miserable. These illnesses often come with fatigue, lack of appetite and concentration difficulties. Sufferers often just want to be left alone many people even experience sadness and anxiety.</p>
<p>Researchers have uncovered why that is. When your body is under attack by a pathogen, some of your immune cells recognise the pathogen and take action to eliminate the threat. To be successful, they need to rally other immune cells as well as several organs of your body. </p>
<p>To do so, they secrete specific proteins, called cytokines. These are messengers, communicating the presence of a pathogen throughout your body, including to <a href="https://www.nature.com/articles/s41586-022-05161-7">your brain</a>.</p>
<p>Once the cytokine signal reaches your brain, it triggers <a href="https://www.sciencedirect.com/science/article/abs/pii/S014976341730893X">changes in the activity of many brain structures</a>. This leads to the development of fever, but not only that. </p>
<p>These brain changes also lead you to <a href="https://www.nature.com/articles/nrn2297">feel and act differently</a>: you are much less motivated to do things you usually like and would rather be alone and in bed. Ultimately, you feel fatigued and you lack appetite. But you can also be more sensitive to negative stimuli, which can easily make you sad and anxious. </p>
<figure class="align-center ">
<img alt="An illustration of a sick person with a blanket on and a thermometer in the mouth, surrounded by four thought bubbles" src="https://images.theconversation.com/files/567852/original/file-20240104-21-7j5303.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/567852/original/file-20240104-21-7j5303.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=394&fit=crop&dpr=1 600w, https://images.theconversation.com/files/567852/original/file-20240104-21-7j5303.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=394&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/567852/original/file-20240104-21-7j5303.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=394&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/567852/original/file-20240104-21-7j5303.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=495&fit=crop&dpr=1 754w, https://images.theconversation.com/files/567852/original/file-20240104-21-7j5303.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=495&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/567852/original/file-20240104-21-7j5303.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=495&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">The feelings of sickness are triggered by your immune system.</span>
<span class="attribution"><span class="source">Credit: Julie Lasselin; sick person: brgfx/Freepik</span>, <a class="license" href="http://creativecommons.org/licenses/by-sa/4.0/">CC BY-SA</a></span>
</figcaption>
</figure>
<p>That means that the psychological experience of sickness is not just triggered by your brain or the pathogen itself – it seems to be unleashed by your own immune system.</p>
<h2>Making people sick for one day</h2>
<p>How can we make sure that the feelings of sickness are really triggered by our own immune system, and not the pathogen? Researchers have actually shown that such feelings can be brought about without a true pathogen being present.</p>
<p>My research group, and a few others in the world, purposely activate the natural immune defences of healthy and young volunteers, without using a pathogen. In several of our experiments, we <a href="https://www.nature.com/articles/s41380-020-00869-2">injected</a> more than 100 study participants with a small dose of lipopolysaccharide, a component of the membrane of the bacteria <em>Escherichia Coli</em>. Because immune cells recognise this component as a pathogenic threat (although no real bacteria are actually present), they get activated and produce cytokines. </p>
<p>As during a real infection, but without the presence of a pathogen, the cytokine signal reaches the brain and triggers behavioural changes together with the feelings of sickness (collectively called <a href="https://www.sciencedirect.com/science/article/pii/S2666354621001824">“sickness behaviour”</a>).</p>
<p>Interestingly, our participants reported the same symptoms – malaise, <a href="https://www.sciencedirect.com/science/article/abs/pii/S0889159119304507">fatigue</a> and <a href="https://karger.com/nim/article/30/1/250/864454/How-Can-Experimental-Endotoxemia-Contribute-to-Our">body pain</a> – without fighting an infection. In the photos below, you can actually see that <a href="https://royalsocietypublishing.org/doi/10.1098/rspb.2017.2430">they look less well after the injection</a>.</p>
<p>The participants said they would rather be at home than in our study room, and were no longer interested in performing the various tasks we asked them to do. And although they were not specifically anxious or sad before the injection, several of the participants reported <a href="https://www.sciencedirect.com/science/article/abs/pii/S0889159116300034">feeling anxious</a> and <a href="https://www.sciencedirect.com/science/article/abs/pii/S0149763418302161">morose</a> afterwards. </p>
<p>Because there were no real bacteria in the blood, and because the liver and immune cells rapidly clear bacterial components from the blood, the production of cytokines lasted only a few hours, typically five to eight hours. And the sickness feelings, including the strong negative emotions that were triggered only a few hours earlier, also <a href="https://karger.com/nim/article/30/1/268/864451/Endotoxin-Induced-Physiological-and-Psychological">subsided within this time frame</a>.</p>
<h2>Why do we feel miserable during infections?</h2>
<p>The question now is: must we feel sick during an infection? And if so, why? Well, even if you are not fully aware of it, fighting a pathogen requires an incredible amount of energy. Both the activity of your immune cells and the increase in body temperature take a heavy toll. The only way your body can cope with these high energy demands is by strongly reducing the activity of organs that are not immediately needed. </p>
<p>Sickness feelings ultimately ensure that your body energy <a href="https://link.springer.com/chapter/10.1007/7854_2022_363">is not used</a> for activities that are not essential at the time of an infection – you need to be calm and stay at home. Thus, they help you avoid using your muscles and even your brain – making you skip the gym or extensive studying. And feeling sad and anxious prevents you from wanting to go out and party with your friends.</p>
<p>The feelings of sickness are therefore <a href="https://www.sciencedirect.com/science/article/abs/pii/S0149763488800046">likely to be beneficial in the fight against the pathogen</a>. </p>
<p>This is probably the reason why <a href="https://journals.biologists.com/jeb/article/224/9/jeb225847/260576/Sickness-behaviors-across-vertebrate-taxa">all vertebrates</a>, and even invertebrates such as <a href="https://www.frontiersin.org/articles/10.3389/fphys.2016.00261/full">bees</a> and <a href="https://onlinelibrary.wiley.com/doi/10.1111/j.1420-9101.2011.02425.x">ants</a>, behave like we do during infections. </p>
<p>So, it is likely to be difficult to simply think your way out of feeling down when ill. But I hope that this insight will help you take the edge off negative thoughts when confronted with a winter illness. Do not feel guilty or worried about feeling miserable – it’s only natural. </p>
<p>A healthy way to respond might actually to embrace these feelings as a normal response of your body when it needs to fight off pathogens. If you don’t, the chances are you will go on a spiral of guilt, fear and negative emotions that keeps getting worse.</p>
<p>And by the way, if you feel miserable in the days following a vaccination… Don’t worry – it similarly means your immune system is at work.</p><img src="https://counter.theconversation.com/content/219991/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Julie Lasselin receives funding from the Swedish Research Council (vetenskapsrådet), Riksbankens Jubileumsfond, and the Osher center for Integrative Health at Karolinska Institutet.</span></em></p>Research suggests we should embrace feeling down when ill.Julie Lasselin, Researcher in Psychoneuroimmunology, Stockholm UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/2149192024-01-15T13:33:10Z2024-01-15T13:33:10ZWhat if every germ hit you at the exact same time? An immunologist explains<figure><img src="https://images.theconversation.com/files/565348/original/file-20231212-15-ba3kr2.jpg?ixlib=rb-1.1.0&rect=0%2C0%2C2121%2C1412&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Your immune system encounters a legion of potential pathogens every day.</span> <span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/photo/woman-shielding-eyes-by-large-green-coronavirus-royalty-free-image/1250588799">Klaus Vedfelt/DigitalVision via Getty Images</a></span></figcaption></figure><figure class="align-left ">
<img alt="" src="https://images.theconversation.com/files/281719/original/file-20190628-76743-26slbc.png?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/281719/original/file-20190628-76743-26slbc.png?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=293&fit=crop&dpr=1 600w, https://images.theconversation.com/files/281719/original/file-20190628-76743-26slbc.png?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=293&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/281719/original/file-20190628-76743-26slbc.png?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=293&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/281719/original/file-20190628-76743-26slbc.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=368&fit=crop&dpr=1 754w, https://images.theconversation.com/files/281719/original/file-20190628-76743-26slbc.png?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=368&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/281719/original/file-20190628-76743-26slbc.png?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=368&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
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<span class="caption"></span>
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<p><em><a href="https://theconversation.com/us/topics/curious-kids-us-74795">Curious Kids</a> is a series for children of all ages. If you have a question you’d like an expert to answer, send it to <a href="mailto:curiouskidsus@theconversation.com">curiouskidsus@theconversation.com</a>.</em></p>
<hr>
<blockquote>
<p><strong>What would happen if all the diseases in the world hit us at the exact same time? – Gabriella, age 12, Irving, Texas</strong></p>
</blockquote>
<hr>
<p>When I was younger, I would watch “Batman” on my black-and-white television after school. Usually, Batman would face either the Joker, the Penguin, the Puzzler, Catwoman or any one of his usual opponents. However, on some occasions, Batman would have to face them all at the same time.</p>
<p>What would happen if, like Batman, the immune system had to face all of its rivals at once?</p>
<p><a href="https://scholar.google.com/citations?user=6JOQvNwAAAAJ&hl=en">I am an immunologist</a> who teaches the fundamentals of immunology to college undergraduates. My research generally focuses on factors that regulate immune responses and prevent autoimmune diseases – conditions where the immune system attacks your own body. As a scientist studying how we build immunity against pathogens such as the virus that causes COVID-19, understanding how the immune system combats multiple threats at the same time is immensely important to me. </p>
<p>There’s no reason why you can’t come down with strep throat at the same time as when you have a cold. In fact, sometimes fighting off one enemy can leave a hole in your defenses that another opportunistic pathogen can take advantage of.</p>
<h2>BAM! Understanding the rivals</h2>
<p>The first point to consider is what your immune system protects you from. The potential bad guys <a href="https://theconversation.com/immune-cells-that-fight-cancer-become-exhausted-within-hours-of-first-encountering-tumors-new-research-210947">include cancer cells</a> and dangerous microorganisms – including bacteria, viruses, fungi and more – that cause infections. The immune system must also be careful <a href="https://theconversation.com/immune-health-is-all-about-balance-an-immunologist-explains-why-both-too-strong-and-too-weak-an-immune-response-can-lead-to-illness-215217">not to damage</a> healthy cells and beneficial microorganisms that live on and inside you. </p>
<p>You interact with <a href="https://kids.frontiersin.org/articles/10.3389/frym.2022.629355">thousands of microorganisms</a> with every breath of air you take. Is the immune system facing off against all of them? Sort of. </p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/565525/original/file-20231213-27-oegbgf.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="Microscope images of two T regulatory cells wrapped around an antigen-presenting cell" src="https://images.theconversation.com/files/565525/original/file-20231213-27-oegbgf.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/565525/original/file-20231213-27-oegbgf.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=600&fit=crop&dpr=1 600w, https://images.theconversation.com/files/565525/original/file-20231213-27-oegbgf.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=600&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/565525/original/file-20231213-27-oegbgf.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=600&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/565525/original/file-20231213-27-oegbgf.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=754&fit=crop&dpr=1 754w, https://images.theconversation.com/files/565525/original/file-20231213-27-oegbgf.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=754&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/565525/original/file-20231213-27-oegbgf.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=754&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">T regulatory cells (red) determine whether an immune response should be mounted.</span>
<span class="attribution"><a class="source" href="https://flic.kr/p/SjQFf7">NIAID/Flickr</a>, <a class="license" href="http://creativecommons.org/licenses/by/4.0/">CC BY</a></span>
</figcaption>
</figure>
<p>It takes a <a href="https://theconversation.com/how-does-fever-help-fight-infections-theres-more-to-it-than-even-some-scientists-realize-210240">tremendous amount of energy</a> to fight a battle once a rival gains a foothold within your blood or tissues, so your immune system works to <a href="https://theconversation.com/how-do-viruses-get-into-cells-their-infection-tactics-determine-whether-they-can-jump-species-or-set-off-a-pandemic-216139">prevent it from getting in the body</a> in the first place. Your skin, <a href="https://theconversation.com/why-do-our-noses-get-snotty-when-we-are-sick-a-school-nurse-explains-the-powers-of-mucus-212949">snot</a>, saliva and <a href="https://theconversation.com/can-you-cry-underwater-205464">tears</a> form a critical <a href="https://www.ncbi.nlm.nih.gov/books/NBK279396/">first line of defense</a>. This is why <a href="https://doi.org/10.1089%2Fsur.2013.134">burn victims</a> who lose too much skin often die from overwhelming infection – their defensive barriers are too compromised and pathogens pour in.</p>
<p>The immune system greatly prefers <a href="https://theconversation.com/a-pediatric-nurse-explains-the-science-of-sneezing-160970">catching a microbe in snot</a> and blowing it out of your nose, or giving you time to wash it off the skin of your hands, over having to wage a cellular war. Gathering an army of <a href="https://theconversation.com/coronavirus-b-cells-and-t-cells-explained-141888">immune cells</a> to fight pathogens takes a lot of energy and makes you feel awful. </p>
<p>For example, the immune system <a href="https://theconversation.com/how-does-fever-help-fight-infections-theres-more-to-it-than-even-some-scientists-realize-210240">increases your body temperature</a> to make it an uncomfortable place for microorganisms to live and grow, but that fever can also make you want to lie down for days.</p>
<h2>BOOM! Where are their weaknesses?</h2>
<p>When Batman faced multiple opponents, he would find a weakness shared by all of the opponents and target it to foil their plans. The immune system uses the exact same strategy.</p>
<p>Certain microbes are considered pathogens largely because they are in the wrong place – such as inside your body instead of on your skin – and causing damage. Pathogens have specific parts on their surfaces called <a href="https://doi.org/10.1038/s41392-021-00687-0">pathogen associated molecular patterns, or PAMPs</a>.</p>
<p>Very importantly, your body doesn’t make PAMPS. This means if your immune system comes across a PAMP, it knows it isn’t supposed to be there and will mount an attack. Because the same PAMP is present on many different pathogens, a strategy to combat one PAMP can defeat many pathogens.</p>
<p>There are molecules in cells all over your body that can recognize PAMPS and destroy anything those PAMPS are on. It’s as though your immune system set up booby traps that can only attack your enemies.</p>
<p>Many of those booby traps are <a href="https://doi.org/10.1038/35100529">toll-like receptors</a>. This family of molecules is located on the surface and inside of many of your cells. Once microbes contact these booby traps, they trigger an alarm that warn other cells of potential danger. In technical terms, this alarm is <a href="https://theconversation.com/what-is-inflammation-two-immunologists-explain-how-the-body-responds-to-everything-from-stings-to-vaccination-and-why-it-sometimes-goes-wrong-193503">called inflammation</a>.</p>
<h2>SPLAT! Raising an army of defenders</h2>
<p>Whereas Batman would need to think of a new strategy to combat the Joker, the Penguin and Catwoman, your immune system devised a plan long ago. </p>
<p>When the virus that causes COVID-19 emerged in 2019, it was something people’s immune systems likely had never seen before. However, some people already had immune cells that could target components of the virus. How is that possible?</p>
<p>The immune system makes many immune cells that are specific to antigens, or unique and recognizable parts of cancers and microorganisms, it hasn’t encountered before. This occurs through a process where pieces of your DNA <a href="https://doi.org/10.1038/nri2941">randomly recombine to form</a> unique immune cell receptors. The DNA in each of these immune cells is different from the DNA in any other cell in your body. Researchers believe that each person can generate <a href="https://www.ncbi.nlm.nih.gov/books/NBK27140/">at least a trillion different combinations</a> of immune receptors, which is <a href="https://doi.org/10.1038/nrmicro2644">more than the number of pathogens</a> an average person would ever face in their lifetime overall.</p>
<figure>
<iframe width="440" height="260" src="https://www.youtube.com/embed/Na-Zc-xWCLE?wmode=transparent&start=0" frameborder="0" allowfullscreen=""></iframe>
<figcaption><span class="caption">Your immune system can churn out billions of unique antibodies.</span></figcaption>
</figure>
<p>Although the immune system makes a lot of immune cells, most of them aren’t used because you’re not exposed to the antigen they’re made to recognize. However, when an immune cell recognizes an antigen, it rapidly <a href="https://bio.libretexts.org/Bookshelves/Microbiology/Microbiology_(Boundless)/11%3A_Immunology/11.07%3A_Antibodies/11.7C%3A_Clonal_Selection_of_Antibody-Producing_Cells">makes many copies of itself</a>. Since pathogens can also multiply rapidly, clonal selection allows you to rapidly raise an army to fight them.</p>
<p>Usually this strategy works well with <a href="https://theconversation.com/when-covid-19-or-flu-viruses-kill-they-often-have-an-accomplice-bacterial-infections-187056">one or two coinfections</a>, such as if you have the common cold and an eye infection at the same time. But what if you were infected with a trillion pathogens at the same time? It would take a tremendous amount of energy and time to build an appropriate army against each microorganism all at once. Unfortunately, the immune system likely would be overwhelmed by this challenge, and you would probably die. </p>
<p>Fortunately, your immune system – like Batman – usually figures out the best way to shift a battle against rivals to its favor, pulling out a victory in the final minutes of the episode.</p>
<hr>
<p><em>Hello, curious kids! Do you have a question you’d like an expert to answer? Ask an adult to send your question to <a href="mailto:curiouskidsus@theconversation.com">CuriousKidsUS@theconversation.com</a>. Please tell us your name, age and the city where you live.</em></p>
<p><em>And since curiosity has no age limit – adults, let us know what you’re wondering, too. We won’t be able to answer every question, but we will do our best.</em></p><img src="https://counter.theconversation.com/content/214919/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Joseph Larkin III receives funding from the Grayson Jockey Research Foundation, The National Institutes of Health, and industry. </span></em></p>Your immune system is often able to fend off pathogens it’s never seen before. But defending your body against all of them all at once is a tough challenge.Joseph Larkin III, Associate Professor of Microbiology and Cell Science, University of FloridaLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/2183072023-12-21T11:58:11Z2023-12-21T11:58:11ZWhy IBD is so hard to treat – and how scientists are making progress<figure><img src="https://images.theconversation.com/files/564472/original/file-20231208-21-jio13j.jpg?ixlib=rb-1.1.0&rect=8%2C8%2C5455%2C3628&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">IBD can be debilitating </span> <span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/illustration-intestine-internal-organs-womens-body-1828134221">Emily frost/Shutterstock</a></span></figcaption></figure><p>Inflammatory bowel disease (IBD) is a <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5478758/">life altering</a> chronic illness that is <a href="https://bmjopen.bmj.com/content/13/3/e065186">rising dramatically globally</a>. It is stubbornly difficult to treat, and many people find the treatments we have just don’t work for them. </p>
<p>Over the last 30 years, there has been almost a 50% increase in cases – now affecting around 5 million people. Not to be confused with irritable bowel syndrome (IBS) which is a condition that affects the digestive system, IBD is more serious. It is the term for two severe illnesses called <a href="https://www.nhs.uk/conditions/crohns-disease/">Crohn’s disease</a> and <a href="https://www.nhs.uk/conditions/ulcerative-colitis/">ulcerative colitis</a>. More women are <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9958616/#:%7E:text=Male%20predominance%20in%20IBD.,%2C%202.32%3A1%20in%20CD.">diagnosed with Crohn’s disease</a> while more men are affected by ulcerative colitis. </p>
<p>People with IBD can experience a variety of <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4106026/">symptoms</a>, ranging from diarrhoea and blood in the stool, to weight loss and belly aches. On paper, this may sound no worse than mild food poisoning, however, this is no normal stomach upset. </p>
<p>Experiences are often extreme; people with IBD can suffer excruciating pain and in some cases, <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9963331/">require surgery</a> to remove parts of the bowel. This is done by redirecting the bowel to a hole in the abdomen, where faeces are collected in a <a href="https://www.nhs.uk/conditions/colostomy/">colostomy bag</a>. </p>
<p>However, we still don’t fully understand the cause of IBD. </p>
<h2>The impact of inflammation</h2>
<p>The main symptom of IBD is excessive and uncontrolled <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5805548/">inflammation</a> – normally a sign of the body fighting off an infection. Although inflammation is an important aspect of our immune system, in IBD it is happening when the body is not under attack. Since we don’t know what causes this over-the-top reaction, <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8720971/">treatments</a> are limited to managing the <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3964397/">derailed immune system</a>. </p>
<figure class="align-center ">
<img alt="Man holds his abdomen." src="https://images.theconversation.com/files/566014/original/file-20231215-17-6sqtab.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/566014/original/file-20231215-17-6sqtab.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=450&fit=crop&dpr=1 600w, https://images.theconversation.com/files/566014/original/file-20231215-17-6sqtab.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=450&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/566014/original/file-20231215-17-6sqtab.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=450&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/566014/original/file-20231215-17-6sqtab.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=566&fit=crop&dpr=1 754w, https://images.theconversation.com/files/566014/original/file-20231215-17-6sqtab.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=566&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/566014/original/file-20231215-17-6sqtab.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=566&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">Many people with IBD are still in pain after treatment.</span>
<span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/men-stomach-pain-causes-abdominal-include-2134025051">onstockphoto/Shutterstock</a></span>
</figcaption>
</figure>
<p><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8373857/">Inflammation is controlled</a> by cell signalling. Our cells detect bacteria using receptors that attach to parts of bacteria. This activates the receptor, causing it to send a signal to proteins, and each protein sends on more signals, creating a signal cascade. This is what tells the body it’s under attack. </p>
<p>Many treatments follow the strategy of intercepting signals and preventing the signal cascade from starting. However, they are <a href="https://journals.lww.com/co-gastroenterology/abstract/2022/07000/management_of_refractory_inflammatory_bowel.6.aspx">not effective</a> for many people. </p>
<p>Scientists are trying to target a different protein network, called <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2924159/">NOD2</a>, that often goes haywire in people with IBD but is not targeted by current treatments. A protein, called <a href="https://www.frontiersin.org/articles/10.3389/fphar.2021.650403/full">RIPK2</a>, seems like a promising target since it is <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6939834/">only found</a> in this network. Researchers from the <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10485824/">European Molecular Biology Laboratory</a> are investigating its structure to help scientists design a new medication that will block the signals from this protein. </p>
<h2>Importance of the microbiome</h2>
<p>Another inspiration for new treatments comes from the bacteria residing in our guts. This community of bacteria, called the gut microbiome, has been associated with <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6314516/">all sorts of health conditions</a> ranging from asthma to obesity. </p>
<p>Gut bacteria work closely with our bodies and play a vital role in digesting food and managing our <a href="https://www.nature.com/articles/s41422-020-0332-7">immune system</a>. In a healthy person, there is a <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4143175/">fine balance</a> between gut bacteria and the immune system. Disruption of this balance can lead to disease, starting from minor discomfort to more severe, long-term conditions. </p>
<p>Scientists are trying to understand how our bodies interact with gut bacteria, and <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8102608/">what changes</a> when people develop IBD. </p>
<p>The gut microbiome is an ecosystem. Just like a forest has animals eating different things, microbes can form a <a href="https://www.frontiersin.org/articles/10.3389/fevo.2019.00153/full">food web</a>. Some bacteria will use up one type of food, while others feed off other foods. Some rely on the waste of other bacteria after they’ve eaten. It is now believed that disruption to the gut microbiome is a characteristic of IBD and contributes to its development and progression.</p>
<p>It’s a chicken and egg situation. Is there a change in the bacteria and food web that alters our bodies? Or does something else in the body, like our immune system, change the food web, subsequently limiting which bacteria can grow? Scientists aren’t sure of the answer. </p>
<p>Instead of trying to figure out what happens first, a team at the <a href="https://www.nature.com/articles/s41467-023-42112-w">Hudson Institute of Medical Research</a> in Australia have focused on investigating which interactions in the food web are the most affected in IBD. This could help scientists to prioritise certain gut bacteria, or their food source, to restore the balance in the microbiome and improve patients’ symptoms. </p>
<p>Hopefully, this specialised targeting of the microbiome will lead to more effective and longer lasting treatments. </p>
<p>Although we have a long way to go before these ideas for treatments can become a reality, it is a step in the right direction. Targeting a new signalling pathway will hopefully control the inflammation in more patients. And studying the microbiome may reveal how we can reverse changes associated with IBD.</p>
<p>Since they are key features of IBD, these developments could allow doctors to stop the disease in the early stages and reduce complications.</p><img src="https://counter.theconversation.com/content/218307/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Falk Hildebrand receives funding from the Biotechnology and Biological Sciences Research Council (BBSRC), European Research Council, Bill & Melinda Gates Foundation and Natural Environment Research Council (NERC).</span></em></p><p class="fine-print"><em><span>Katarzyna Sidorczuk receives funding from the Biotechnology and Biological Sciences Research Council (BBSRC) and European Research Council H2020 StG.</span></em></p><p class="fine-print"><em><span>Wing Koon receives funding from the UKRI Medical Research Council for the Microbes, Microbiomes, and Bioinformatics Doctoral Training Partnership as a CASE Award in collaboration with Oxford Nanopore Technologies.</span></em></p>The current treatments for inflammatory bowel disease do not work for everyone. Tapping into new areas of biology may be the key to developing new therapies.Falk Hildebrand, Researcher in Bioinformatician, Quadram InstituteKatarzyna Sidorczuk, Research Scientist in Metagenomics, Quadram InstituteWing Koon, PhD student in Bioinformatics, Quadram InstituteLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/2161392023-11-21T13:26:58Z2023-11-21T13:26:58ZHow do viruses get into cells? Their infection tactics determine whether they can jump species or set off a pandemic<figure><img src="https://images.theconversation.com/files/560185/original/file-20231117-23-zg89fr.jpg?ixlib=rb-1.1.0&rect=0%2C0%2C2309%2C1299&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Surface proteins on a virus enable it to attach to and get inside a cell to start replicating.</span> <span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/photo/new-omicron-sub-variant-bq-1-1-royalty-free-image/1435658319">koto_feja/E+ via Getty Images</a></span></figcaption></figure><p>COVID-19, flu, mpox, noroviral diarrhea: How do the viruses that cause these diseases actually infect you?</p>
<p>Viruses <a href="https://www.khanacademy.org/science/biology/biology-of-viruses/virus-biology/a/intro-to-viruses">cannot replicate on their own</a>, so they must infect cells in your body to make more copies of themselves. The life cycle of a virus can thus be roughly described as: get inside a cell, make more virus, get out, repeat. </p>
<p>Getting inside a cell, or <a href="https://doi.org/10.1016/j.jmb.2018.03.034">viral entry</a>, is the part of the cycle that most vaccines target, as well as a key barrier for viruses jumping from one species to another. <a href="https://scholar.google.com/citations?user=OQ7vzu0AAAAJ&hl=en">My lab</a> and many others study this process to better anticipate and combat emerging viruses.</p>
<h2>How viruses enter cells</h2>
<p>Different viruses travel into the body in <a href="https://www.oregon.gov/oha/ph/diseasesconditions/communicabledisease/pages/transmission.aspx">various ways</a> – via airborne droplets, on food, through contact with mucous membranes or through injection. They typically first infect host cells near their site of entry – the cells lining the respiratory tract for most airborne viruses – then either remain there or spread throughout the body.</p>
<p>Viruses <a href="https://doi.org/10.1016/j.jmb.2018.06.024">recognize specific proteins or sugars</a> on host cells and stick to them. Each virus gets only one shot at putting its genome inside a cell – if their entry machinery misfires, they risk becoming inactivated. So they <a href="https://doi.org/10.1016/j.virol.2015.02.037">use several mechanisms</a> to prevent triggering entry prematurely.</p>
<p>After the virus binds to the cell, specific molecules on the cell’s surface or within the cell’s recycling machinery <a href="https://doi.org/10.1111/tra.12389">activate viral coat proteins for entry</a>. An example is the SARS-CoV-2 spike that COVID-19 vaccines target. These proteins need to modify the cell membrane to allow the viral genome to get through without killing the cell in the process. Different viruses use different tricks for this, but most work like cellular secretion – how cells release materials into their environment – in reverse. Specialized viral proteins help <a href="https://doi.org/10.1146/annurev-virology-111821-093413">merge the membranes of the virus and the cell</a> together and release the viral core into the interior of the cell.</p>
<figure>
<iframe width="440" height="260" src="https://www.youtube.com/embed/i__QSjC-pt0?wmode=transparent&start=0" frameborder="0" allowfullscreen=""></iframe>
<figcaption><span class="caption">This animation depicts HIV fusing its membrane with a cell in order to release its contents inside.</span></figcaption>
</figure>
<p>At this point, the viral genome can enter the cell and <a href="https://doi.org/10.1016%2FB978-0-12-800947-5.00004-1">start replicating</a>. Some viruses use only the cell’s machinery to replicate, while others carry along portions of their own replication machinery and borrow some parts from the cell. After replicating their genomes, viruses assemble the components required to make new viruses.</p>
<p>Two central questions scientists are studying about viral entry are how your body’s defenses can disrupt it and what determines whether a virus from other species can infect people.</p>
<h2>Immune defenses against viruses</h2>
<p>Your body has a multilayered defense system against viral threats. But the part of your immune system called the <a href="https://doi.org/10.1016/j.jaci.2009.12.980">antibody response</a> is generally thought to be most effective at <a href="https://doi.org/10.1016/j.immuni.2022.10.017">sterilizing immunity</a> – preventing an infection from taking hold in the first place as opposed to just limiting its scope and severity. </p>
<p>For many viruses, antibodies target the part of the virus that binds to cells. This is the case not just for current COVID-19 vaccines but also the majority of immunity against influenza, whether from vaccines or from prior infection. </p>
<p>However, some antibodies target the entry machinery instead: Rather than preventing the virus from sticking, they prevent the virus from working altogether. Such antibodies are often harder for the viruses to escape from but are difficult to reproduce with vaccines. For that reason, developing antibodies that inhibit cell entry has the been the goal of many <a href="https://doi.org/10.1016/j.coviro.2016.02.002">next-generation vaccine efforts</a>.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/551885/original/file-20231003-25-cv0pnn.png?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="Diagram of the mechanisms of four classes of HIV antivirals" src="https://images.theconversation.com/files/551885/original/file-20231003-25-cv0pnn.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/551885/original/file-20231003-25-cv0pnn.png?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=496&fit=crop&dpr=1 600w, https://images.theconversation.com/files/551885/original/file-20231003-25-cv0pnn.png?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=496&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/551885/original/file-20231003-25-cv0pnn.png?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=496&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/551885/original/file-20231003-25-cv0pnn.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=623&fit=crop&dpr=1 754w, https://images.theconversation.com/files/551885/original/file-20231003-25-cv0pnn.png?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=623&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/551885/original/file-20231003-25-cv0pnn.png?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=623&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">This diagram shows how four different classes of antiviral drugs inhibit HIV. One stops viruses from entering cells, and three inhibit different viral enzymes.</span>
<span class="attribution"><a class="source" href="https://commons.wikimedia.org/wiki/File:HIV-drug-classes.svg">Thomas Splettstoesser/Wikimedia Commons</a>, <a class="license" href="http://creativecommons.org/licenses/by-sa/4.0/">CC BY-SA</a></span>
</figcaption>
</figure>
<h2>Species-hopping and pandemics</h2>
<p>The other key question researchers are asking about viral entry is <a href="https://www.cdc.gov/flu/pandemic-resources/national-strategy/risk-assessment.htm">how to tell when</a> a virus from another species poses a threat to people. This is particularly important because many viruses are first identified in animals such as bats, birds and pigs before they spread to humans, but it’s unclear which ones may cause a pandemic.</p>
<p>The part of viruses that stick to human cells varies the most across species, while the part that gets the virus into cells <a href="https://doi.org/10.1016/bs.aivir.2016.08.004">tends to stay mostly the same</a>. Many researchers have thought that viruses changing in ways that bind better to human cells, like influenza viruses that bind to cells in the nose and throat, are some of the most important warning signs for pandemic risk. </p>
<p>However, coronaviruses – the family of viruses containing SARS-CoV-2 – are prompting re-examination of that idea. This is because several animal coronaviruses can actually <a href="https://doi.org/10.1038/s41564-020-0688-y">bind to human cells</a>, but only a few seem to be able to transmit well between people.</p>
<p>Only time will tell whether researchers need to broaden their pandemic prevention horizons or if their current prioritization of risky viruses is correct. The one grim reality of pandemic research, like earthquake research, is that there will always be another one – we just don’t know when or where, and we <a href="https://www.niaid.nih.gov/sites/default/files/pandemic-preparedness-plan.pdf">want to be ready</a>.</p><img src="https://counter.theconversation.com/content/216139/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Peter Kasson receives funding from the National Institutes of Health, the National Science Foundation, the Commonwealth Health Research Board, and the Knut and Alice Wallenberg Foundation. He is affiliated with the University of Virginia, Uppsala University, and Georgia Institute of Technology.</span></em></p>Viruses can get into cells in several ways. Figuring out how to stop them from entering in the first place is a key to developing better vaccines and stopping future pandemics.Peter Kasson, Professor of Molecular Physiology and Biomedical Engineering, University of VirginiaLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/2152172023-11-20T13:18:45Z2023-11-20T13:18:45ZImmune health is all about balance – an immunologist explains why both too strong and too weak an immune response can lead to illness<figure><img src="https://images.theconversation.com/files/559704/original/file-20231115-15-wutiiv.png?ixlib=rb-1.1.0&rect=0%2C0%2C2044%2C1593&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">When immune cells become overactive, your immune system itself can cause disease.</span> <span class="attribution"><a class="source" href="https://flic.kr/p/2oHpNSe">NIAID/Flickr</a>, <a class="license" href="http://creativecommons.org/licenses/by-sa/4.0/">CC BY-SA</a></span></figcaption></figure><p>For immune health, some influencers seem to think the Goldilocks philosophy of “just right” is overrated. Why settle for less immunity when you can have more? Many social media posts push supplements and other life hacks that “boost your immune system” to keep you healthy and fend off illness.</p>
<p>However, these claims are not based on science and what is known about immune function. Healthy immune systems don’t need to be “boosted.” Instead, the immune system works best when it is <a href="https://doi.org/10.1038/ni.2430">perfectly balanced</a>. Scientific experts on the immune system – immunologists – know that too much of an immune reaction could result in allergies, autoimmune disorders or <a href="https://theconversation.com/what-is-inflammation-two-immunologists-explain-how-the-body-responds-to-everything-from-stings-to-vaccination-and-why-it-sometimes-goes-wrong-193503">chronic inflammation</a>. On the flip side, <a href="https://theconversation.com/immunocompromised-people-make-up-nearly-half-of-covid-19-breakthrough-hospitalizations-an-extra-vaccine-dose-may-help-166241">too little of an immune reaction</a> could result in illness or infection.</p>
<p>Your immune system requires a delicate balance to operate properly. When it’s out of balance, your immune system itself can cause disease.</p>
<h2>Cellular balance</h2>
<p>The immune system is the mobile defense system of your body. It is a complex network of cells and organs that work together to protect your body from infection and disease. Your immune cells are continually on patrol, traveling throughout your body looking for infectious invaders and damage. </p>
<p>New immune cells are created in your bone marrow. Certain immune cells – called <a href="https://theconversation.com/coronavirus-b-cells-and-t-cells-explained-141888">B and T cells</a> – are the special forces of the immune system, playing an important role in the elimination of infectious invaders. Because of this role, these cells undergo a rigorous boot camp during their development to ensure they will not discharge friendly fire on healthy cells in the body. </p>
<figure>
<iframe width="440" height="260" src="https://www.youtube.com/embed/PSRJfaAYkW4?wmode=transparent&start=0" frameborder="0" allowfullscreen=""></iframe>
<figcaption><span class="caption">Your immune system is an extensive network of cells and many other components that constantly surveil your body.</span></figcaption>
</figure>
<p>Any <a href="https://doi.org/10.1038/nri.2017.19">B cell</a> or <a href="https://doi.org/10.1146/annurev-immunol-101320-022432">T cell</a> exhibiting activity against the self – or autoreactivity – is killed during training. Millions of newly created B and T cells are killed every day because they fail this training process. If these self-reactive cells escape destruction, they could turn against the body and carry out an inappropriate <a href="https://doi.org/10.1038/ni.3731">autoimmune attack</a>. </p>
<p><a href="https://scholar.google.com/citations?view_op=list_works&hl=en&hl=en&user=PGIEO34AAAAJ">My research</a> investigates how B cells are able to slip past the checkpoints the immune system has in place to guard against autoreactivity. These <a href="https://doi.org/10.1172/jci12462">tolerance checkpoints</a> ensure that autoreactive immune cells are either purged from the body or held in permanent lockdown and unable to engage in inappropriate responses that would target healthy tissue.</p>
<h2>More isn’t necessarily better</h2>
<p>You’ve likely seen advertisements for dietary supplements that promise to “boost immune function.” While this may sound appealing, it is important to keep in mind that the immune system functions best when perfectly balanced.</p>
<p>If the immune system is like a thermostat, turning it up too high results in overactivation and uncontrolled inflammation, while turning it down too low results in a failure to respond to infection and disease. </p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/559701/original/file-20231115-23-d6qlle.png?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="Diagram of immune activation scale in the shape of a rainbow wedge, with 'vulnerable to infection' at the smaller end, 'sweet spot' in the middle, and 'autoimmunity' at the larger end" src="https://images.theconversation.com/files/559701/original/file-20231115-23-d6qlle.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/559701/original/file-20231115-23-d6qlle.png?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=260&fit=crop&dpr=1 600w, https://images.theconversation.com/files/559701/original/file-20231115-23-d6qlle.png?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=260&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/559701/original/file-20231115-23-d6qlle.png?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=260&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/559701/original/file-20231115-23-d6qlle.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=326&fit=crop&dpr=1 754w, https://images.theconversation.com/files/559701/original/file-20231115-23-d6qlle.png?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=326&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/559701/original/file-20231115-23-d6qlle.png?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=326&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Too much or too little immune activation can lead to illness.</span>
<span class="attribution"><a class="source" href="https://commons.wikimedia.org/wiki/File:Inflammation_scale.svg">Kevbonham/Wikimedia Commons</a>, <a class="license" href="http://creativecommons.org/licenses/by-sa/4.0/">CC BY-SA</a></span>
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</figure>
<p>Because sustaining <a href="https://www.nature.com/collections/mxwslsscsf">immune balance</a> is critical, tinkering with the immune system through the use of supplements is not a good idea unless you have a clinical deficiency in certain vital nutrients. For people with healthy levels of nutrients, taking supplements could lead to a false sense of security, particularly since the fine print on the back of supplements usually has <a href="https://www.fda.gov/food/information-consumers-using-dietary-supplements/questions-and-answers-dietary-supplements">this disclaimer</a> about their listed benefits: “This statement has not been evaluated by the FDA. Not intended to diagnose, treat, cure, or prevent any disease.”</p>
<p>Eating a <a href="https://www.hsph.harvard.edu/nutritionsource/nutrition-and-immunity/">well-balanced diet</a>, exercising regularly, reducing stress and getting decent sleep, on the other hand, can help your body maintain a functioning and healthy immune system. Although these lifestyle behaviors are not foolproof, they contribute to overall good health and ultimately to a more healthy immune system.</p>
<p>In reality, <a href="https://doi.org/10.1080/07853890.2017.1407035">vaccines are the only safe and effective tool</a> beyond healthy lifestyle behaviors to support your immune system. Vaccines contain harmless forms of pathogens that help to train your immune cells to recognize and fight them. When you come into contact with the real and harmful version of the pathogen out in the wild – whether it’s at a grocery store, social event or school – at a later date, these fully trained immune memory cells will immediately begin to fight and destroy the pathogen, sometimes so quickly that you don’t even realize you’ve been infected.</p>
<p>In a world where people are continually bombarded by the marketing mantra that more is better, rest assured that when it comes to the immune system, maintaining perfect balance is just right.</p><img src="https://counter.theconversation.com/content/215217/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Aimee Pugh Bernard is affiliated with Immunize Colorado and Colorado Immunization Advocates as an unpaid board member.</span></em></p>Dietary supplements claim to be able to ‘boost your immune system’ to combat disease. But attaining immune balance through a healthy lifestyle and vaccination is a safer bet to keep in good health.Aimee Pugh Bernard, Assistant Professor of Immunology and Microbiology, University of Colorado Anschutz Medical CampusLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/2129492023-11-06T13:33:20Z2023-11-06T13:33:20ZWhy do our noses get snotty when we are sick? A school nurse explains the powers of mucus<figure><img src="https://images.theconversation.com/files/548367/original/file-20230914-21-s25lth.jpg?ixlib=rb-1.1.0&rect=1%2C0%2C1196%2C797&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Use a tissue and wash your hands after a booger explosion.</span> <span class="attribution"><a class="source" href="https://www.flickr.com/photos/schwachs/4352350750/">Joshua Wachs/Flickr</a>, <a class="license" href="http://creativecommons.org/licenses/by-nc-nd/4.0/">CC BY-NC-ND</a></span></figcaption></figure><figure class="align-left ">
<img alt="" src="https://images.theconversation.com/files/281719/original/file-20190628-76743-26slbc.png?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/281719/original/file-20190628-76743-26slbc.png?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=293&fit=crop&dpr=1 600w, https://images.theconversation.com/files/281719/original/file-20190628-76743-26slbc.png?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=293&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/281719/original/file-20190628-76743-26slbc.png?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=293&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/281719/original/file-20190628-76743-26slbc.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=368&fit=crop&dpr=1 754w, https://images.theconversation.com/files/281719/original/file-20190628-76743-26slbc.png?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=368&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/281719/original/file-20190628-76743-26slbc.png?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=368&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
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<p><em><a href="https://theconversation.com/us/topics/curious-kids-us-74795">Curious Kids</a> is a series for children of all ages. If you have a question you’d like an expert to answer, send it to <a href="mailto:curiouskidsus@theconversation.com">curiouskidsus@theconversation.com</a>.</em></p>
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<p><strong>Why do our noses get snotty when we are sick? – Veronica P., age 5, Panama City, Florida</strong></p>
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<p>Not many things are as uncomfortable and annoying as a runny or congested nose when you’re sick. Constantly blowing your nose and not being able to breathe through it may leave you wondering: Why does this happen? </p>
<p>I’m a nurse practitioner who works with kids every day and also <a href="https://stories.purdue.edu/kristin-ahrens/">teaches nursing</a>. The answer is pretty simple. Mucus – or snot – is one of the ways your body helps keep you healthy. </p>
<p>Mucus lines your nose, throat, lungs and other parts of your body to protect it from bad bacteria, viruses and other particles. Your body <a href="https://www.everydayhealth.com/mucus/">continuously creates mucus</a> to fight off germs and help get rid of them. </p>
<p>When you’re sick, your immune system ramps up to produce extra mucus to flush out germs. While it might seem gross, mucus is also pretty amazing.</p>
<h2>Slimy protector</h2>
<p>Your body creates mucus out of a combination of <a href="https://www.britannica.com/science/mucus">water, proteins and salts</a>. Its sticky consistency traps bad microorganisms and other unwanted particles, like dust, pet dander and mildew, so they can’t get farther into your system. </p>
<p>Some components in mucus <a href="https://www.nibib.nih.gov/news-events/newsroom/disarming-bacteria-mucus-and-phages">stop bacteria from banding together</a> and becoming more dangerous. Other elements can actually <a href="https://doi.org/10.1007/BF02976990">kill the invaders</a> that are trying to make you sick. And though scientists don’t completely understand how, the <a href="https://doi.org/10.1007/BF02976990">proteins and genes in mucus</a> seem to work together to make it thicker and stickier if necessary.</p>
<p>Once germs or other potentially damaging particles are trapped and neutralized, your body’s way of getting rid of them altogether is to make so much mucus that you have to blow, sneeze or cough them out. </p>
<p>You might have noticed that sometimes when you’re sick, your nose can get red too. This is because your immune system, in addition to making mucus, also sends extra white blood cells to the source of an infection. As they rush to the scene to help fight infection, the extra white blood cells <a href="https://my.clevelandclinic.org/health/articles/21196-immune-system/">expand the blood vessels</a> in the area, making your nose look red. All the wiping and blowing can make it red, too.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/548373/original/file-20230914-9125-jab4s8.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="A chart displaying mucus colors from clear to black and describing what each means." src="https://images.theconversation.com/files/548373/original/file-20230914-9125-jab4s8.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/548373/original/file-20230914-9125-jab4s8.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=960&fit=crop&dpr=1 600w, https://images.theconversation.com/files/548373/original/file-20230914-9125-jab4s8.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=960&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/548373/original/file-20230914-9125-jab4s8.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=960&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/548373/original/file-20230914-9125-jab4s8.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=1206&fit=crop&dpr=1 754w, https://images.theconversation.com/files/548373/original/file-20230914-9125-jab4s8.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=1206&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/548373/original/file-20230914-9125-jab4s8.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=1206&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
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<span class="caption">The mucus rainbow.</span>
<span class="attribution"><a class="source" href="https://riseandshine.childrensnational.org/snot-colors-and-what-they-mean/">Children's National Hospital</a>, <a class="license" href="http://creativecommons.org/licenses/by-nc-sa/4.0/">CC BY-NC-SA</a></span>
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<p>Snot can come in a rainbow of yucky colors. When white blood cells are fighting an infection, they release chemicals that may <a href="https://www.healthline.com/health/snot-color#white-snot">turn your snot yellow</a>. When more of those cells are needed to get the job done, mucus can even turn green. Typically, after a few days, colored mucus changes back to clear and your stuffy nose will go away. </p>
<h2>Not just in your nose</h2>
<p>Mucus isn’t found just in your nose and lungs.</p>
<p>Your <a href="https://theconversation.com/can-you-cry-underwater-205464">eyes also have a thin layer of mucus</a> that helps protect them from particles in the air. When you get sick or get an eye infection, <a href="https://www.verywellhealth.com/eye-mucus-types-3422108">eye mucus</a> can act the same way it does in your nose – catching and killing germs. Eye mucus can also sometimes turn thick and yellow. If that happens, you’ll want to call your health care provider. Don’t ever touch your eyes with your fingers. That can <a href="https://www.nyoph.com/blog/this-is-why-you-shouldnt-rub-your-eyes/">introduce more germs</a>.</p>
<p>Your stomach and intestines also have protective mucus. If you’ve ever had an upset stomach that led to diarrhea, the mucus in your intestinal track was working overtime to help <a href="https://doi.org/10.1038/nrgastro.2013.35">flush out bad bacteria</a>. That’s why your normal poop goes from a solid mush to something more slimy. There are other reasons you can have stomachaches – like stress, constipation or food allergies – but if you have diarrhea, your mucus is definitely hard at work. </p>
<h2>Animals have it too</h2>
<p>Humans aren’t the only animals that use mucus. For example, <a href="https://petriage.com/clinical-insights/your-pets-mucous-membranes/">dogs and cats have mucus</a> too.</p>
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<a href="https://images.theconversation.com/files/548831/original/file-20230918-31-zzsqlo.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="A brightly colored fish is surrounded by a mucus cocoon on the sea floor next to some rocks. A smaller fish is nearby." src="https://images.theconversation.com/files/548831/original/file-20230918-31-zzsqlo.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/548831/original/file-20230918-31-zzsqlo.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/548831/original/file-20230918-31-zzsqlo.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/548831/original/file-20230918-31-zzsqlo.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/548831/original/file-20230918-31-zzsqlo.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/548831/original/file-20230918-31-zzsqlo.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/548831/original/file-20230918-31-zzsqlo.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=503&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
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<span class="caption">Some fish use mucus for protection while sleeping.</span>
<span class="attribution"><a class="source" href="https://commons.wikimedia.org/wiki/File:Abrolhos_Marine_National_ParkRobertoCostaPinto20.jpg">RobertoCostaPinto/WikiMedia Commons</a>, <a class="license" href="http://creativecommons.org/licenses/by-sa/4.0/">CC BY-SA</a></span>
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<p><a href="https://www.montereybayaquarium.org/stories/mucus-slime-snot">Parrotfish</a>, <a href="https://doi.org/10.1098/rsbl.2010.0916">wrasses</a> and <a href="https://cimi.org/blog/mucus-in-the-animal-kingdom/">other sea creatures</a> produce mucus cocoons to help protect them from predators at night. </p>
<p>Chameleons use the sticky <a href="https://www.nationalgeographic.com/animals/article/chameleon-tongue-mucus-sticky-animals">mucus on the end of their tongues</a> to reel in their prey. Earthworms secrete mucus to help them move through the soil, which in turn <a href="https://doi.org/10.5194/egusphere-egu2020-17611">benefits the soil</a>.</p>
<p>In humans, mucus helps neutralize and eliminate the microbial bad guys. So the next time you reach for a tissue to blow your nose, remember: Your body’s natural defenses are doing their best to keep you healthy or make you better. Just think of all that snot as one of your body’s superpowers.</p>
<hr>
<p><em>Hello, curious kids! Do you have a question you’d like an expert to answer? Ask an adult to send your question to <a href="mailto:curiouskidsus@theconversation.com">CuriousKidsUS@theconversation.com</a>. Please tell us your name, age and the city where you live.</em></p>
<p><em>And since curiosity has no age limit – adults, let us know what you’re wondering, too. We won’t be able to answer every question, but we will do our best.</em></p><img src="https://counter.theconversation.com/content/212949/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Kristin Ahrens is a member of the National Association of Pediatric Nurse Practitioners (NAPNAP) and the National Association of School Nurses (NASN). </span></em></p>Slimy snot is an important part of how your immune system wards off germs and fights back from infection.Kristin Ahrens, Pediatric Nurse Practitioner, Adjunct Instructor of Nursing at Purdue Global, Purdue UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/2153262023-10-13T18:04:37Z2023-10-13T18:04:37ZAn itching paradox – a molecule that triggers the urge to scratch also turns down inflammation in the skin<figure><img src="https://images.theconversation.com/files/553357/original/file-20231011-23-fpzuw.jpg?ixlib=rb-1.1.0&rect=0%2C0%2C2168%2C1381&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Itching, and the subsequent urge to scratch, can make eczema worse.</span> <span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/photo/scratching-chest-royalty-free-image/1463546524">Kinga Krzeminska/Moment via Getty Images</a></span></figcaption></figure><p>Itching can be uncomfortable, but it’s a normal part of your skin’s immune response to external threats. When you’re itching from an encounter with poison ivy or mosquitoes, consider that your urge to scratch may have evolved to get you to <a href="https://doi.org/10.1083/jcb.201603042">swat away disease-carrying pests</a>. </p>
<p>However, for many people who suffer from chronic skin diseases like eczema, the sensation of itch can <a href="https://eczema.org/information-and-advice/living-with-eczema/itching-and-scratching/">fuel a vicious cycle</a> of scratching that interrupts sleep, reduces productivity and <a href="https://nationaleczema.org/eczema-emotional-wellness/">prevents them from enjoying daily life</a>. This cycle is caused by <a href="https://nationaleczema.org/blog/why-does-eczema-itch/#">sensory neurons and skin immune cells</a> working together to promote itching and skin inflammation.</p>
<p>But, paradoxically, some of the mechanisms behind this feedback loop also stop inflammation from getting worse. In our newly published research, my team of immunologists and neuroscientists <a href="https://profiles.ucsf.edu/marlys.fassett">and I</a> discovered that a specific type of itch-sensing neuron can <a href="https://www.science.org/doi/10.1126/sciimmunol.abi6887">push back on the itch-scratch-inflammation cycle</a> in the presence of a small protein. This protein, called <a href="https://doi.org/10.1016/j.jaci.2013.10.048">interleukin-31, or IL-31</a>, is typically involved in triggering itching. </p>
<p>This negative feedback loop – like the vicious cycle – is only possible because the itch-sensing nerve endings in your skin are closely intertwined with the millions of cells that <a href="https://doi.org/10.4049/jimmunol.1801473">make up your skin’s immune system</a>.</p>
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<figcaption><span class="caption">Your skin has its own immune system.</span></figcaption>
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<h2>IL-31: An itchy molecule</h2>
<p>The protein IL-31 is key to the connection between the nervous and immune systems. This molecule is <a href="https://doi.org/10.1038/ni1084">produced by some immune cells</a>, and like other <a href="https://my.clevelandclinic.org/health/body/24585-cytokines">members of this molecule family</a>, it specializes in helping immune cells communicate with each other. </p>
<p>IL-31 is rarely present in the skin or blood of people who don’t have a history of eczema, allergies, asthma or related conditions. But those with conditions like eczema that cause chronic itch have significantly <a href="https://doi.org/10.3389/fmed.2021.638325">increased skin production of IL-31</a>. There is strong evidence that IL-31 is one of a small set of proteins that immune cells produce that can bind directly to sensory neurons and <a href="https://doi.org/10.1016/j.cell.2013.08.057">trigger itching</a>. Small amounts of purified IL-31 injected directly into skin or spinal fluid leads to impressively <a href="https://doi.org/10.1016/j.jaci.2013.10.048">rapid-onset itching and scratching</a>.</p>
<p>However, when my colleagues and I induced rashes in mice by exposing them to dust mites, we found that itch-sensing neurons turned down the dial on inflammation at the site of itching instead of promoting it. They did so by secreting <a href="https://doi.org/10.1007/978-1-61779-310-3_1">small molecules called neuropeptides</a> that, in this context, directed immune cells to respond less enthusiastically. In sum, we had discovered an inverse relationship between itching and skin inflammation, tethered by a single molecule.</p>
<p>But if IL-31 triggers itching, which can worsen inflammation by making patients scratch their skin, how does it reduce inflammation? </p>
<p>We found the answer to this paradox in a little-known function of sensory neurons called <a href="https://www.sciencedirect.com/topics/medicine-and-dentistry/neurogenic-inflammation">neurogenic inflammation</a>. This nerve reflex triggers sensory neurons to release various signaling molecules directly into tissues, including <a href="https://doi.org/10.1111/1523-1747.ep12455620">specific neuropeptides that promote signs of inflammation</a> like increased blood flow to the skin. Neurogenic inflammation acts within the same nerves that transmit sensory information like itch, pain, touch and temperature, but differs by the path it takes: away from the brain rather than toward it.</p>
<p>We discovered that IL-31 can induce neurogenic inflammation, <a href="https://www.science.org/doi/10.1126/sciimmunol.abi6887">mapping a direct pathway</a> going from IL-31 through sensory neurons to repress immune cells in the skin. When we engineered mice to be unresponsive to IL-31, we similarly found that they had more activated skin immune cells that produced more inflammation. This means the net effect of IL-31 is to blunt overall inflammation.</p>
<h2>IL-31 as potential treatment</h2>
<p>Our study shows that IL-31 causes sensory neurons in the skin to perform <a href="https://www.science.org/doi/10.1126/sciimmunol.abi6887">two very different functions</a>: They signal inward to the spinal cord and brain to stimulate an itching sensation that typically leads to more inflammation, but they also signal back out to the skin and quell inflammation by inhibiting certain immune cells.</p>
<p>Although paradoxical, this makes evolutionary sense. Scratching an itch can feel very satisfying but doesn’t have much utility in the modern world where we’re more likely to suffer from compulsive scratching than encounter stinging nettles. In contrast, unchecked inflammation underlies many chronic autoimmune diseases. Therefore, turning off an immune response in inflamed tissue can be as important as turning it on.</p>
<p>Our discoveries raise important questions about the implications of modifying IL-31 to treat different diseases. For one, it isn’t clear how IL-31-sensing neurons interface with <a href="https://doi.org/10.1038/s41590-019-0493-z">other neuronal circuits</a> that also regulate skin inflammation. Furthermore, some patients have <a href="https://doi.org/10.1056/NEJMoa1606490">higher levels of allergic proteins</a> in their blood or <a href="https://doi.org/10.1111/jdv.17218">develop asthma flares</a> when taking existing drugs that target IL-31. IL-31 is also found in some lung and gut cells – how and why would an itch-inducing molecule be present in internal organs? </p>
<p>Anatomical niches where sensory neurons and immune cells converge are present throughout the human body. If an itchy molecule like IL-31 can use neuronal circuitry to dampen an immune response in the skin, similar molecules like those used in <a href="https://migrainetrust.org/live-with-migraine/healthcare/treatments/gepants/">migraine drugs</a> could be repurposed to treat skin conditions, too.</p><img src="https://counter.theconversation.com/content/215326/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Marlys Fassett receives funding from the National Institutes of Health/National Institute of Arthritis, Musculoskeletal and Skin Diseases. She also serves as a grant reviewer for the National Eczema Association.</span></em></p>Itch-sensing neurons in your skin are intertwined with your immune cells. Counterintuitively, the molecule that connects them triggers responses that both worsen and improve skin conditions.Marlys Fassett, Associate Professor of Dermatology, University of California, San FranciscoLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/2116512023-10-11T12:29:43Z2023-10-11T12:29:43ZYour immune system makes its own antiviral drug − and it’s likely one of the most ancient<figure><img src="https://images.theconversation.com/files/552140/original/file-20231004-23-x2ljhp.jpg?ixlib=rb-1.1.0&rect=0%2C0%2C2309%2C1299&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Blocking viruses from replicating their RNA is one way antivirals work.</span> <span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/photo/coronavirus-single-rna-strand-microscopic-view-of-royalty-free-image/1275277285">CROCOTHERY/iStock via Getty Images Plus</a></span></figcaption></figure><p>Antiviral drugs are generally considered to be a 20th century invention. But recent research has uncovered an unexpected facet to your immune system: It can <a href="https://doi.org/10.1038/s41586-018-0238-4">synthesize its own antiviral molecules</a> in response to viral infections. </p>
<p><a href="https://lsa.umich.edu/chem/people/faculty/nmarsh.html">My laboratory</a> studies a protein that makes these natural antiviral molecules. Far from a modern human invention, nature evolved cells to make their own “drugs” as the <a href="https://doi.org/10.1074/jbc.REV120.012784">earliest defense against viruses</a>. </p>
<h2>How antivirals work</h2>
<p>Viruses have no independent life cycle – they are <a href="https://theconversation.com/think-like-a-virus-to-understand-why-the-pandemic-isnt-over-yet-and-what-the-us-needs-to-do-to-help-other-countries-161400">completely dependent</a> on the cells they infect to supply all the chemical building blocks needed to replicate themselves. Once inside a cell, the virus hijacks its machinery and turns it into a factory to make hundreds of new viruses.</p>
<p><a href="https://www.britannica.com/science/antiviral-drug">Antiviral drugs</a> are molecules that inactivate proteins essential to the functioning of the virus by exploiting the fundamental differences in the way that cells and viruses replicate. </p>
<p>One key difference between cells and most viruses is how they store their genetic information. All <a href="https://theconversation.com/the-human-genome-project-pieced-together-only-92-of-the-dna-now-scientists-have-finally-filled-in-the-remaining-8-176138">cells use DNA</a> to store their genetic information. DNA is a long, chainlike molecule built from four different chemical building blocks, each representing a different “letter” of the genetic code. These building blocks are connected by chemical bonds in a head-to-tail fashion to produce strings of millions of letters. The order of these letters spells out the genetic blueprint for building a new cell.</p>
<p>Many viruses, however, store their genetic information <a href="https://theconversation.com/were-viruses-around-on-earth-before-living-cells-emerged-a-microbiologist-explains-197880">using RNA</a>. RNA is built from a chain of four chemical letters, just like DNA, but the letters have slightly different molecular structures. RNA is single-stranded, while DNA is double-stranded. Viral genomes are also much smaller than cellular genomes, typically only a few thousand letters long.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/551885/original/file-20231003-25-cv0pnn.png?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="Diagram of the mechanisms of four classes of HIV antivirals" src="https://images.theconversation.com/files/551885/original/file-20231003-25-cv0pnn.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/551885/original/file-20231003-25-cv0pnn.png?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=496&fit=crop&dpr=1 600w, https://images.theconversation.com/files/551885/original/file-20231003-25-cv0pnn.png?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=496&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/551885/original/file-20231003-25-cv0pnn.png?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=496&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/551885/original/file-20231003-25-cv0pnn.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=623&fit=crop&dpr=1 754w, https://images.theconversation.com/files/551885/original/file-20231003-25-cv0pnn.png?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=623&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/551885/original/file-20231003-25-cv0pnn.png?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=623&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">This diagram shows how four different classes of antiviral drugs inhibit HIV. One stops viruses from entering cells, and three inhibit different viral enzymes.</span>
<span class="attribution"><a class="source" href="https://commons.wikimedia.org/wiki/File:HIV-drug-classes.svg">Thomas Splettstoesser/Wikimedia Commons</a>, <a class="license" href="http://creativecommons.org/licenses/by-sa/4.0/">CC BY-SA</a></span>
</figcaption>
</figure>
<p>When a virus replicates, it makes many copies of its RNA genome using a protein called <a href="https://theconversation.com/messenger-rna-how-it-works-in-nature-and-in-making-vaccines-166975">RNA polymerase</a>. The polymerase starts at one end of the existing RNA chain and “reads” the string of chemical letters one at a time, selecting the appropriate building block and adding it to the growing strand of RNA. This process is repeated until the entire sequence of letters has been copied to form a new RNA chain.</p>
<p>One <a href="https://doi.org/10.1007/978-981-13-9073-9_22">class of antiviral drugs</a> interferes with the RNA copying process in a cunning way. The head-to-tail construction of the RNA chain requires each chemical letter to have two connection points – a head to connect to the previous letter and a tail to allow the following letter to be added on. These antivirals mimic one of the chemical letters but crucially lack the tail connection point. If the RNA polymerase mistakes the drug for the intended chemical letter and adds it to the growing RNA chain, the copying process stops because there is nothing to attach the next letter to. For this reason, this type of antiviral drug is called a chain-terminating inhibitor. </p>
<h2>Viperin as antiviral producer</h2>
<p>Previously, researchers thought that chain-terminating antiviral drugs were strictly a product of human ingenuity, developed from advances in scientific understanding of viral replication. However, the discovery that a protein in your cells <a href="https://doi.org/10.1074/jbc.REV120.012784">named viperin</a> synthesizes a natural chain-terminating antiviral has revealed a new side of your immune system. </p>
<p>Viperin works by chemically removing the tail connection point from one of the four RNA building blocks of a virus’s genome. This converts the building block into a chain-terminating antiviral drug. </p>
<p>This strategy has proved to be highly effective for treating viral infections. For example, the <a href="https://theconversation.com/in-the-fight-against-coronavirus-antivirals-are-as-important-as-a-vaccine-heres-where-the-science-is-up-to-133926">COVID-19 antiviral remdesivir</a> works in this way. A viral RNA polymerase has to join together many thousands of letters to copy a virus’s genome, but an antiviral drug has to fool it only once to derail its copying. An incomplete genome lacks the necessary instructions to make a new virus and becomes useless. </p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/552129/original/file-20231004-25-kvjat4.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="Illustration of Remdesivir blocking a viral RNA polymerase from replicating RNA" src="https://images.theconversation.com/files/552129/original/file-20231004-25-kvjat4.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/552129/original/file-20231004-25-kvjat4.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=450&fit=crop&dpr=1 600w, https://images.theconversation.com/files/552129/original/file-20231004-25-kvjat4.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=450&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/552129/original/file-20231004-25-kvjat4.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=450&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/552129/original/file-20231004-25-kvjat4.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=566&fit=crop&dpr=1 754w, https://images.theconversation.com/files/552129/original/file-20231004-25-kvjat4.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=566&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/552129/original/file-20231004-25-kvjat4.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=566&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Remdesivir (red, center) works by blocking a viral RNA polymerase (blue) from replicating RNA (violet and orange).</span>
<span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/photo/remdesivir-coronavirus-drug-and-target-illustration-royalty-free-image/1307403157">Juan Gaertner/Science Photo Library via Getty Images</a></span>
</figcaption>
</figure>
<p>Moreover, although cells also have their own polymerases, they never replicate RNA like viruses do. This potentially allows chain-terminating antiviral drugs to <a href="https://doi.org/10.1007/978-981-13-9073-9_22">selectively inhibit viral replication</a>, reducing unwanted side effects. </p>
<p>Clearly, viperin does not fully protect against all RNA viruses – otherwise no RNA viruses would make you sick. It seems that some viral RNA polymerases, such as those <a href="https://doi.org/10.1038/s41586-018-0238-4">in poliovirus</a>, have evolved to discriminate against the antiviral molecules that viperin synthesizes and blunt their effect. However, viperin is only one arm of your <a href="https://theconversation.com/explainer-how-the-human-body-first-fights-off-pathogens-80532">immune system</a>, which includes specialized cells and proteins that protect you from infection in other ways.</p>
<h2>Ancient antivirals</h2>
<p>Scientists <a href="https://doi.org/10.1073/pnas.011593298">discovered viperin</a> about 20 years ago while searching for genes that turn on in response to viral infections. However, figuring out what viperin actually does proved very challenging. </p>
<p>Viperin’s function was particularly puzzling because it resembles an ancient group of proteins called <a href="https://doi.org/10.1021/cr4004709">radical SAM enzymes</a> that are usually found in bacteria and molds. Notably, radical SAM enzymes are extremely rare in animals. Exposure to air rapidly inactivates them, and researchers thought they likely didn’t work in people. It’s still unclear how viperin avoids inactivation.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/551896/original/file-20231003-23-yg2y0k.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="Diagram showing structure of viperin without (left) and with (right) an antiviral bound in its center. The structure with the antiviral is more tightly wound in its center." src="https://images.theconversation.com/files/551896/original/file-20231003-23-yg2y0k.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/551896/original/file-20231003-23-yg2y0k.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=228&fit=crop&dpr=1 600w, https://images.theconversation.com/files/551896/original/file-20231003-23-yg2y0k.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=228&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/551896/original/file-20231003-23-yg2y0k.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=228&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/551896/original/file-20231003-23-yg2y0k.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=287&fit=crop&dpr=1 754w, https://images.theconversation.com/files/551896/original/file-20231003-23-yg2y0k.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=287&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/551896/original/file-20231003-23-yg2y0k.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=287&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">This illustration shows the structure of viperin without (left) and with (right) an antiviral bound in its center.</span>
<span class="attribution"><a class="source" href="https://doi.org/10.1074/jbc.REV120.012784">Soumi Ghosh and Neil Marsh/Journal of Biological Chemistry</a>, <a class="license" href="http://creativecommons.org/licenses/by-sa/4.0/">CC BY-SA</a></span>
</figcaption>
</figure>
<p>Researchers were <a href="https://doi.org/10.1038/s41586-018-0238-4">clued in to viperin’s function</a> when they noticed that the gene coding for viperin is next to a gene involved in synthesizing one of RNA’s building blocks. This observation led them to examine whether viperin might modify this RNA building block. </p>
<p>Following this discovery, researchers identified <a href="https://doi.org/10.1038/s41586-020-2762-2">viperinlike proteins</a> across all kingdoms of life, from ancient bacteria to modern plants and animals. This meant that viperin is a very ancient protein that evolved early in life, probably well before the advent of multicellular organisms – because even <a href="https://theconversation.com/viruses-are-both-the-villains-and-heroes-of-life-as-we-know-it-169131">bacteria must fight viral infections</a>. </p>
<p>As more complex life forms evolved, viperin was retained and integrated into the complex immune systems of modern animals. Thus, this most recently discovered arm of your immune system’s defenses against viruses is <a href="https://doi.org/10.1074/jbc.REV120.012784">likely the most ancient</a>.</p><img src="https://counter.theconversation.com/content/211651/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Neil Marsh receives funding from the National Institute of General Medical Sciences to support his laboratory's work on viperin. </span></em></p>The human body has been making antivirals for eons, long before scientists did. A protein in your cells called viperin produces molecules that work similarly to the COVID-19 antiviral remdesivir.Neil Marsh, Professor of Chemistry and Biological Chemistry, University of MichiganLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/2085382023-09-21T21:27:36Z2023-09-21T21:27:36ZLyme disease: The pathogen’s cunning strategies for persistent infection offer clues for vaccine development<figure><img src="https://images.theconversation.com/files/547386/original/file-20230911-25-n5os9t.JPG?ixlib=rb-1.1.0&rect=65%2C23%2C1709%2C1158&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">The black-legged tick is the vector that spreads Lyme disease. Its bite can infect humans with the Borrelia burgdorferi bacterium.</span> <span class="attribution"><span class="source">(Jim Gathany/CDC)</span></span></figcaption></figure><iframe style="width: 100%; height: 100px; border: none; position: relative; z-index: 1;" allowtransparency="" allow="clipboard-read; clipboard-write" src="https://narrations.ad-auris.com/widget/the-conversation-canada/lyme-disease-the-pathogens-cunning-strategies-for-persistent-infection-offer-clues-for-vaccine-development" width="100%" height="400"></iframe>
<p>Lyme disease is the leading <a href="https://www.who.int/news-room/fact-sheets/detail/vector-borne-diseases">vector-borne disease</a> — meaning diseases that are transmitted to humans from another organism like a tick or mosquito — in <a href="https://doi.org/10.1186/s12889-019-7069-6">North America and Europe</a>. </p>
<p><a href="https://doi.org/10.3201/eid2702.202731">New human cases are estimated</a> at over <a href="http://dx.doi.org/10.15585/mmwr.ss6622a1">400,000 in the United States each year</a>. Canada has experienced a drastic increase in human cases, <a href="https://www.canada.ca/en/public-health/services/diseases/lyme-disease/surveillance-lyme-disease.html#a5">from 266 cases in 2011 to 3,147 in 2021</a>, as the habitat of its vector, a tick, expands north. </p>
<p>The initial symptoms of human Lyme disease can be vague, such as fever, headache, fatigue and often rash. It is a potentially serious condition that can affect multiple systems in the body — including the heart, nervous system and joints — and can become a chronic illness.</p>
<p>Lyme disease is caused by a unique, spiral-shaped (spirochete) bacterium called <a href="https://doi.org/10.1099/00207713-34-4-496"><em>Borrelia burgdorferi</em></a>. <em>B. burgdorferi</em> cannot survive in the environment on its own. For <a href="https://doi.org/10.21775/cimb.042.473">survival and transmission</a>, it requires susceptible hosts (usually small mammals or birds) and a <a href="https://doi.org/10.1056/NEJM198303313081301">specific vector</a>: the black-legged tick, also called the deer tick.</p>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/535388/original/file-20230703-257464-m0lz6y.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/535388/original/file-20230703-257464-m0lz6y.png?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=420&fit=crop&dpr=1 600w, https://images.theconversation.com/files/535388/original/file-20230703-257464-m0lz6y.png?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=420&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/535388/original/file-20230703-257464-m0lz6y.png?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=420&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/535388/original/file-20230703-257464-m0lz6y.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=528&fit=crop&dpr=1 754w, https://images.theconversation.com/files/535388/original/file-20230703-257464-m0lz6y.png?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=528&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/535388/original/file-20230703-257464-m0lz6y.png?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=528&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">Lyme disease infectious cycle: Adult ticks lay egg sacs that can hatch thousands of tick larvae. Larvae are not born with Borrelia burgdorferi but can acquire the bacterium when they feed on an infected host. After feeding, larvae molt to nymphs which must feed once to molt to adults. Female adult ticks also feed once before laying the egg sac. Nymphs and adult ticks can transmit B. burgdorferi to susceptible hosts while feeding.</span>
<span class="attribution"><span class="source">(BioRender)</span></span>
</figcaption>
</figure>
<h2>Evading the immune system</h2>
<p><em>B. burgdorferi</em> must survive extremely diverse conditions over the course of its transmission and infection cycle: from host to tick vector, and then into new hosts. </p>
<p>This bacterium senses and responds to its surroundings, most notably by <a href="https://doi.org/10.1128/iai.70.7.3382-3388.2002">modifying its appearance</a> by changing the <a href="https://doi.org/10.1073/pnas.92.7.2909" title="). _B. burgdorferi_ has over [50 surface-exposed proteins](https://doi.org/10.1128/jb.00658-16 "">proteins on its outer surface</a> to <a href="https://doi.org/10.1111/j.1574-695X.2012.00980.x">help it survive</a> in either <a href="https://doi.org/10.1038/s41467-023-35897-3">the tick</a> or the host.</p>
<p>When a tick infected by <em>B. burgdorferi</em> bites and feeds on a vertebrate host, it provides a signal for the bacteria to switch its proteins to those required to infect the host, and to begin migrating through the tick and into the bite site. This process takes between <a href="https://doi.org/10.4269/ajtmh.1995.53.397">36 and 72 hours</a>. </p>
<p>However, many of these proteins are recognized by the host as foreign, and the host’s immune system works to try to clear the infection. This includes a strong, antibody response targeted against <em>B. burgdorferi</em>. </p>
<p>Despite these immune responses, <em>B. burgdorferi</em> is able to cause long-term infections. In natural host reservoirs — the animals that the bacterium usually finds itself in via tick bites, such as small rodents — these infections do not cause diseases like those seen in humans and other <a href="https://doi.org/10.1016/j.idc.2007.12.013">non-natural reservoirs</a>. </p>
<p>In fact, the bacteria itself does not produce any products that would be <a href="https://doi.org/10.1016/j.cll.2015.07.004">toxic to its hosts</a>, either natural or non-natural. Yet chronic infection in humans can lead to <a href="https://doi.org/10.1038/nrdp.2016.90">Lyme neuroborreliosis, carditis and Lyme arthritis</a>.</p>
<figure class="align-center ">
<img alt="Bacteria that look like bright green and yellow squiggles against a dark green background" src="https://images.theconversation.com/files/548570/original/file-20230915-23-4ysjok.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/548570/original/file-20230915-23-4ysjok.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=612&fit=crop&dpr=1 600w, https://images.theconversation.com/files/548570/original/file-20230915-23-4ysjok.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=612&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/548570/original/file-20230915-23-4ysjok.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=612&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/548570/original/file-20230915-23-4ysjok.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=770&fit=crop&dpr=1 754w, https://images.theconversation.com/files/548570/original/file-20230915-23-4ysjok.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=770&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/548570/original/file-20230915-23-4ysjok.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=770&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">Microscopic image of Lyme disease bacteria Borrelia burgdorferi. In this photo, immunofluorescent antibodies have been used to change the colour of spirochetes that express different outer surface proteins.</span>
<span class="attribution"><span class="source">(NIAID)</span>, <a class="license" href="http://creativecommons.org/licenses/by/4.0/">CC BY</a></span>
</figcaption>
</figure>
<p>How then, are these bacteria able to cause such a devastating disease in humans and other animals, but not in their natural host reservoirs?</p>
<p>While there is still much to learn about <em>B. burgdorferi</em>, we know of several factors that play a role in the <a href="https://doi.org/10.1038/nrdp.2016.90">range of disease it causes</a>. These include:</p>
<ul>
<li>its genetic make-up, </li>
<li>its ability to access various tissues (such as the joints, heart and nervous system) due to its <a href="https://doi.org/10.1128/iai.01228-12">ability to move around (motility)</a>, and </li>
<li>the immune response of the host. </li>
</ul>
<p>Apart from motility, <em>B. burgdorferi</em> also protects itself from the strong <em>B. burgdorferi</em>-specific targeted antibody response of its host’s immune system by changing the appearance of the main outer surface protein expressed during persistent infection in a process called <a href="https://doi.org/10.1128/iai.66.8.3698-3704.1998">antigenic variation</a>.</p>
<h2>How Lyme disease is perpetuated</h2>
<p>In addition to antigenic variation, <em>B. burgdorferi</em> bacteria can also change their DNA by <a href="https://doi.org/10.1073/pnas.0402745101">exchanging genetic information, a process also known as gene transfer</a>. This process allows these bacteria to further alter their <a href="https://doi.org/10.1128/mbio.00153-10">appearance</a> <a href="https://doi.org/10.1534/genetics.111.130773">during infection</a> to avoid the host immune system.</p>
<p>This process works so well that these <em>B. burgdorferi</em> bacteria appear different enough to allow <a href="https://doi.org/10.7326/0003-4819-127-2-199707150-00006">re-infection</a> or even <a href="https://doi.org/10.1128/iai.01817-14">co-infection</a> (where multiple strains of B. burgdorferi infect a single host at the same time) of a vertebrate host, like a mouse or a human, despite the presence of specific antibodies to fight the bacterium.</p>
<p>In fact, in nature, the majority of host reservoirs and the ticks that carry the bacterium are infected with <a href="https://doi.org/10.1128/AEM.02296-15">multiple strains of <em>B. burgdorferi</em></a>. The ability of <em>B. burgdorferi</em> to reinfect and co-infect both ticks and hosts increases the spread of the bacteria in the environment as well as the chances that humans will encounter Lyme disease.</p>
<h2>Human cases of Lyme disease are increasing</h2>
<p>As a vector-borne pathogen, <em>B. burgdorferi</em> only infects individuals that are bitten by an infected tick. It is not transmitted from <a href="https://doi.org/10.1093/cid/ciz872">person to person</a>.</p>
<p>Environments that support black-legged/deer ticks are at risk of harbouring <em>B. burgdorferi</em>. In North America, these species of ticks are widely distributed throughout the eastern and midwestern United States. Recent <a href="https://doi.org/10.1093/jme/tjy104">geographic expansion</a> to the north is increasing the prevalence of Lyme disease <a href="https://doi.org/10.1503/cmaj.080148">in Canada</a>. </p>
<p>The increase of human Lyme disease cases highlights the failure of existing preventive strategies — such as minimizing exposure to tick habitats, performing diligent tick checks, and wearing suitable clothing when performing activities in known tick habitats — and emphasizes the need for an effective <a href="https://doi.org/10.21775/cimb.042.191">human vaccine</a>.</p>
<h2>A One Health approach</h2>
<p>At <a href="https://www.vido.org/">Vaccine and Infectious Disease Organization</a> at the University of Saskatchewan, we are taking a <a href="https://ipac-canada.org/one-health">One Health</a> approach by recognizing that human health is closely related to the health of animals and the shared environment. We are investigating the role of <em>B. burgdorferi</em>, ticks, and susceptible animals on the spread and survival of the Lyme disease bacterium. </p>
<p>It is important to mimic the natural infectious cycle as much as possible when identifying potential vaccine and drug targets. This is because the way host animals are infected (for example, artificial needle infection or natural tick bite) can produce drastic differences in the resulting infection. </p>
<p>Additionally, despite the prevalence of this disease, there are still many aspects of the infectious cycle that remain unknown due to the uniqueness of <em>B. burgdorferi</em> and a lack of knowledge about the tick vector. </p>
<p>For example, we recently learned that a <em>B. burgdorferi</em> protein is responsible for regulating the components necessary for the bacterium to infect vertebrates, including humans. The absence of this protein, among other things, leads to the <a href="https://doi.org/10.1038/s41467-023-35897-3">death of <em>B. burgdorferi</em> in ticks</a>, making it an exciting target for research investigation. </p>
<p>By learning more about the molecular mechanisms that change or reduce the severity of the disease caused by this bacterium, we can identify new targets for the prevention of human Lyme disease.</p><img src="https://counter.theconversation.com/content/208538/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Jenny Wachter does not work for, consult, own shares in or receive funding from any company or organisation that would benefit from this article, and has disclosed no relevant affiliations beyond their academic appointment.</span></em></p>The bacterium that causes Lyme disease is a master of disguise, changing its appearance to evade the immune system as it moves from the ticks that carry it to humans or animals.Jenny Wachter, Research scientist/Adjunct professor, University of SaskatchewanLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/2102402023-09-11T12:34:57Z2023-09-11T12:34:57ZHow does fever help fight infections? There’s more to it than even some scientists realize<figure><img src="https://images.theconversation.com/files/547038/original/file-20230907-17-4s7zuu.jpg?ixlib=rb-1.1.0&rect=0%2C0%2C2121%2C1412&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Being feverish is unpleasant, but it can help your body overcome invading pathogens.</span> <span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/photo/mother-measuring-the-temperature-of-her-ill-royalty-free-image/1458502274">Narisara Nami/Moment via Getty Images</a></span></figcaption></figure><p>When you’re <a href="https://doi.org/10.1038%2Fnri3843">sick with a fever</a>, your doctor will likely tell you it’s a sign that your immune system is defending you against an infection. Fever typically results from immune cells at infected sites sending chemical signals to the brain to raise the set point of your body’s thermostat. So, you <a href="https://youtu.be/jRvxnpfCDSo">feel chills</a> when the fever starts and feel hot when the fever breaks.</p>
<p>However, if you were to ask your doctor exactly how fever protects you, don’t expect a completely satisfactory answer.</p>
<p>Despite scientific consensus that fever is beneficial in fighting infections, exactly how is contentious. We are a <a href="https://scholar.google.com/citations?user=2o9r-L8AAAAJ&hl=en">veterinary pathologist</a> and an <a href="https://scholar.google.com/citations?user=RI7ng_YAAAAJ&hl=en">emergency physician</a> interested in <a href="https://isemph.org/what-is-evolutionary-medicine">applying evolutionary principles</a> to medical problems. The evolution of fever is a classic conundrum because fever’s effects seem so harmful. Besides making you feel uncomfortable, you may also worry you’ll dangerously overheat. It is also metabolically costly to generate that much heat. </p>
<p>In our research and review, we propose that since fever occurs throughout much of the animal kingdom, this costly response <a href="https://doi.org/10.1093/emph/eoaa044">must have benefits</a> or it never would have evolved or been retained across species over time. We highlight several important but rarely considered points that help explain how the heat of fever helps your body fight infections.</p>
<figure>
<iframe width="440" height="260" src="https://www.youtube.com/embed/jRvxnpfCDSo?wmode=transparent&start=0" frameborder="0" allowfullscreen=""></iframe>
<figcaption><span class="caption">Fever is a physiological response that has persisted for hundreds of millions of years across species.</span></figcaption>
</figure>
<h2>How fever fights infection</h2>
<p>Infections are <a href="https://doi.org/10.1186%2Fs12915-017-0433-z">caused by pathogens</a>. Pathogens can be microbes such as certain species of bacteria, fungi or protozoans. If microbes or viruses have infected your cells and are using them to replicate, your own cells can also be considered pathogens and are treated that way by your immune system.</p>
<p>The main explanation for how fever helps control infections is that <a href="https://theconversation.com/normal-human-body-temperature-is-a-range-around-98-6-f-a-physiologist-explains-why-139270">higher temperatures</a> put heat-induced stress on pathogens, killing them or at least inhibiting their growth. But why would the somewhat higher body temperatures of fever – an increase of about 1.8 to 5.4 degrees Fahrenheit (<a href="https://doi.org/10.1038/nri3843">1 to 4 degrees Celsius</a>) – which can’t even kill your own healthy cells, harm such a wide variety of pathogens?</p>
<p>Immunologists have noted that slight heat <a href="https://doi.org/10.1038/nri3843">makes immune cells work better</a>. The implication is that fever is needed to enhance their defensive function. However, from an evolutionary perspective, it seems strange to require the massive energy cost of generating a fever just to get more activity from immune cells, especially since there are already plentiful and faster molecular signals available to activate them.</p>
<p>In addition to heat, <a href="https://doi.org/10.1186%2Far2632">slightly low oxygen levels</a> and <a href="https://doi.org/10.1155%2F2018%2F1218297">slight acidity</a> <a href="https://doi.org/10.1371/journal.ppat.1000282">also boost</a> immune cell function. Since these stressful conditions also occur at infected sites, it makes sense that immune cells evolved to have their maximum functionality match their stressful working conditions. In fact, since anything in a state of growth is inherently vulnerable to stress – and pathogens are typically growing – researchers, including one of us, have proposed that a function of immune cells is to actively <a href="https://doi.org/10.1098%2Frspb.2016.0266">make local conditions stressful</a> to preferentially harm the growing pathogens.</p>
<h2>Heating up pathogens locally</h2>
<p><a href="https://openstax.org/books/microbiology/pages/17-5-inflammation-and-fever">Inflammation</a> is a local defensive response to infection. It <a href="https://theconversation.com/what-is-inflammation-two-immunologists-explain-how-the-body-responds-to-everything-from-stings-to-vaccination-and-why-it-sometimes-goes-wrong-193503">typically involves</a> heat, pain, redness and swelling in the areas where the immune system is most active. While some scientists are aware that infected sites generate heat, many believe that the feeling of warmth from inflammation is only from dilated blood vessels bringing in warmer blood from core body tissues.</p>
<p>However, researchers have found that inflamed tissues, even in core body tissues, are up to 1.8 to 3.6 F (<a href="https://doi.org/10.1016/j.jacc.2005.11.050">1 to 2 C</a>) warmer than adjacent normal tissues, so warmth is not just a byproduct of more blood flow. Much of that extra heat is coming from the immune cells themselves. When they generate reactive oxygen species to kill pathogens in a process known as the respiratory burst, <a href="https://doi.org/10.1093/infdis/150.3.366">substantial heat</a> is also produced. To date, however, the temperatures involved have not been measured.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/547047/original/file-20230907-19-nezfs6.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="Over-the-shoulder view of someone holding a thermometer reading 38.5 degrees Celsius." src="https://images.theconversation.com/files/547047/original/file-20230907-19-nezfs6.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/547047/original/file-20230907-19-nezfs6.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=401&fit=crop&dpr=1 600w, https://images.theconversation.com/files/547047/original/file-20230907-19-nezfs6.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=401&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/547047/original/file-20230907-19-nezfs6.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=401&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/547047/original/file-20230907-19-nezfs6.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/547047/original/file-20230907-19-nezfs6.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/547047/original/file-20230907-19-nezfs6.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=503&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Even an increase of a few degrees can affect how well your body kills pathogens.</span>
<span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/photo/from-above-sick-lady-looking-at-thermometer-while-royalty-free-image/1393759427">Israel Sebastian/Moment via Getty Images</a></span>
</figcaption>
</figure>
<p>While cells can tolerate a wide range of temperatures, all cells experience a sharp decline in their ability to grow and survive at higher temperatures. For mammalian cells, and presumably the pathogens that infect them, even a single degree or two above temperatures around 113 F (45 C) is <a href="https://doi.org/10.1016/S1040-8428(01)00179-2">almost always deadly</a>. So the heat of fever adds to already warmer local temperatures.</p>
<p>There is evidence that pathogens are exposed to temperatures that are much higher than the body temperature routinely measured with a thermometer in the emergency department. A 2018 study finding that local temperatures can be <a href="https://doi.org/10.1371/journal.pbio.2003992">as high as 122 F (50 C) in mitochondria</a> – the powerhouse of the cell – came as a <a href="https://doi.org/10.1371/journal.pbio.2005113">surprise to researchers</a>. The heat mitochondria generate is put to good use in warming the body and <a href="https://doi.org/10.1016/j.bbi.2020.11.031">for fever</a>. Likewise, we suggest that the local heat the respiratory burst produces at the surface of immune cells helps kill pathogens.</p>
<h2>Heat and other stressors</h2>
<p>Immune cells target pathogens with a <a href="https://doi.org/10.1155/2017/9671604">variety of stressors</a> meant to kill or inhibit them. These include reactive oxygen species, toxic peptides, digestive enzymes, high acidity and nutrient deprivation. Most chemical reactions are sped up by increased temperatures, so it isn’t surprising that heat enhances these defenses.</p>
<p>Researchers have shown heat to be <a href="https://pubmed.ncbi.nlm.nih.gov/34477/">synergistic with low oxygen and acidity</a> in killing pathogens. Notably, neither febrile temperatures nor iron restriction on their own were able to inhibit the growth of the infectious bacteria <a href="https://doi.org/10.1126/science.760197"><em>Pasteurella multocida</em></a>, but they could when combined. The stress of heat doesn’t act alone when controlling infections.</p>
<p>The standard view that the heat of fever kills pathogens and enhances immune responses is correct but incomplete. Fever’s ability to control infections comes from the few extra, but critical, degrees it adds to enhance existing locally generated heat to harm vulnerable growing pathogens. And fever also always acts with other defenses, never alone. </p>
<p>At <a href="https://doi.org/10.1038%2Fnri3843">over 600 million years old</a>, fever is an ancient feature of life on this planet that deserves respect. In fact, you owe it to infection-fighting heat that you are still here – alive – to read this. Something to think about the next time you’re sick.</p><img src="https://counter.theconversation.com/content/210240/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>The authors do not work for, consult, own shares in or receive funding from any company or organization that would benefit from this article, and have disclosed no relevant affiliations beyond their academic appointment.</span></em></p>The heat and chills that come with fever are not only uncomfortable but also metabolically costly. Increased body temperature, however, can make all the difference when you’re sick.Edmund K. LeGrand, Adjunct Professor of Biomedical and Diagnostic Sciences, University of TennesseeJoe Alcock, Professor of Emergency Medicine, University of New MexicoLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/2088022023-08-17T10:50:21Z2023-08-17T10:50:21ZHow biological differences between men and women alter immune responses – and affect women’s health<figure><img src="https://images.theconversation.com/files/539557/original/file-20230726-21-jhiwex.jpg?ixlib=rb-1.1.0&rect=0%2C0%2C3849%2C2568&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">
</span> <span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/wooden-cubes-image-male-female-gender-2175270281">Fida Olga/Shutterstock</a></span></figcaption></figure><p>Most people will have heard the term “man flu”, which refers to men’s perceived tendency to exaggerate the severity of a cold or a similar minor ailment. </p>
<p>What most people may not know is that, generally speaking, women mount stronger <a href="https://pubmed.ncbi.nlm.nih.gov/36121220/">immune responses</a> to infections than men. Men are <a href="https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1005374">more susceptible</a> to infections from, for example, HIV, hepatitis B, and <em>Plasmodium falciparum</em> (the parasite responsible for malaria). </p>
<p>They can also have more severe symptoms, with evidence showing they’re more likely to be <a href="https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1005374">admitted to hospital</a> when infected with hepatitis B, tuberculosis, and <em>Campylobacter jejuni</em> (a bacteria that causes gastroenteritis), among others.</p>
<p>While this may be positive for women in some respects, it also means women are at <a href="https://www.nature.com/articles/nri2815">greater risk</a> of developing chronic diseases driven by the immune system, known as immune-mediated inflammatory diseases.</p>
<hr>
<figure class="align-right ">
<img alt="" src="https://images.theconversation.com/files/542294/original/file-20230811-4652-hn8w80.png?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/542294/original/file-20230811-4652-hn8w80.png?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=600&fit=crop&dpr=1 600w, https://images.theconversation.com/files/542294/original/file-20230811-4652-hn8w80.png?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=600&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/542294/original/file-20230811-4652-hn8w80.png?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=600&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/542294/original/file-20230811-4652-hn8w80.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=754&fit=crop&dpr=1 754w, https://images.theconversation.com/files/542294/original/file-20230811-4652-hn8w80.png?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=754&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/542294/original/file-20230811-4652-hn8w80.png?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=754&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
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<p><em>This article is part of <a href="https://theconversation.com/uk/topics/womens-health-matters-143335">Women’s Health Matters</a>, a series about the health and wellbeing of women and girls around the world. From menopause to miscarriage, pleasure to pain the articles in this series will delve into the full spectrum of women’s health issues to provide valuable information, insights and resources for women of all ages.</em></p>
<p><em>You may be interested in:</em></p>
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<p><em><a href="https://theconversation.com/science-experiments-traditionally-only-used-male-mice-heres-why-thats-a-problem-for-womens-health-205963">Science experiments traditionally only used male mice – here’s why that’s a problem for women’s health</a></em></p>
<hr>
<p>Here we will explore how biological factors influence immune differences between the sexes and how this affects women’s health. While we acknowledge that both sex and gender may affect immune responses, this article will focus on biological sex rather than gender. </p>
<h2>Battle of the sexes</h2>
<p>There are differences <a href="https://www.nature.com/articles/nri.2016.90">between the sexes</a> at every stage of the immune response, from the number of immune cells, to their degree of activation (how ready they are to respond to a challenge), and beyond.</p>
<p>However, the story is more complicated than that. Our immune system evolves throughout our lives, learning from past experiences, but also responding to the physiological challenges of getting older. As a result, <a href="https://www.nature.com/articles/nri.2016.90">sex differences</a> in the immune system can be seen from birth through puberty into adulthood and <a href="https://academic.oup.com/jleukbio/advance-article/doi/10.1093/jleuko/qiad053/7190870">old age</a>.</p>
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<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/discovery-of-gene-associated-with-20-autoimmune-diseases-leads-to-promising-drug-trials-131957">Discovery of gene associated with 20 autoimmune diseases leads to promising drug trials</a>
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</em>
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<p>Why do these differences occur? The first part of answering this question involves the X chromosome. Females have two X chromosomes, while males have one X and one Y chromosome. The <a href="https://pubmed.ncbi.nlm.nih.gov/20651746/">X chromosome</a> contains the largest number of immune-related genes. </p>
<p>The X chromosome also has <a href="https://link.springer.com/article/10.1007/s00018-020-03526-7">around 118 genes</a> from a gene family that are able to stop the expression of other genes, or change how proteins are made, including those required for immunity. These gene-protein regulators are known as microRNA, and there are only <a href="https://pubmed.ncbi.nlm.nih.gov/24808907/">two microRNA genes</a> on the Y chromosome.</p>
<p>The X chromosome has <a href="https://www.genome.gov/about-genomics/fact-sheets/X-Chromosome-facts">more genes overall</a> (around 900) than the Y chromosome (around 55), so female cells have evolved to switch off one of their X chromosomes. This is not like turning off a light switch, but more like using a dimmer. </p>
<p>Around <a href="https://bmcgenomics.biomedcentral.com/articles/10.1186/s12864-019-5507-6">15-25% of genes</a> on the silenced X chromosome are expressed at any given moment in any given cell. This means female cells can often express more immune-related genes and gene-protein regulators than males. This generally means a faster clearance of pathogens in females than males.</p>
<figure class="align-center ">
<img alt="Three women laughing together outdoors." src="https://images.theconversation.com/files/539933/original/file-20230728-19-fesqbz.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/539933/original/file-20230728-19-fesqbz.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/539933/original/file-20230728-19-fesqbz.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/539933/original/file-20230728-19-fesqbz.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/539933/original/file-20230728-19-fesqbz.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/539933/original/file-20230728-19-fesqbz.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/539933/original/file-20230728-19-fesqbz.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=503&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">Women have two X chromosomes, which partly explains why the female immune system works differently.</span>
<span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/mature-female-friends-socializing-backyard-together-583329838">Monkey Business Images/Shutterstock</a></span>
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</figure>
<p>Second, men and women have <a href="https://www.frontiersin.org/articles/10.3389/fimmu.2020.604000/full">varying levels</a> of different sex hormones. Progesterone and testosterone are broadly considered to limit immune responses. While both hormones are produced by males and females, progesterone is found at higher concentrations in non-menopausal women than men, and testosterone is much higher in men than women. </p>
<p>The role of <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6533072/">oestrogen</a>, one of the main female sex hormones, is more complicated. Although generally oestrogen <a href="https://www.sciencedirect.com/science/article/abs/pii/S000887491500026X?via%3Dihub">enhances immune responses</a>, its levels vary during the menstrual cycle, are high in pregnancy and low after menopause. </p>
<p>Due in part to these genetic and hormonal factors, pregnancy and the years following are associated with heightened immune responses to external challenges such as infection. </p>
<p>This has been regarded as an <a href="https://www.nature.com/articles/nri.2016.90">evolutionary feature</a>, protecting women and their unborn children during pregnancy and enhancing the mother’s survival throughout the child-rearing years, ultimately ensuring the survival of the population. We also see this pattern in <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2628977/">other species</a> including insects, lizards, birds and mammals. </p>
<h2>What does this all mean?</h2>
<p>With women’s heightened immune responses to infections comes an increased risk of certain diseases and prolonged immune responses after infections.</p>
<p>An <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3328995/">estimated 75-80%</a> of all immune-mediated inflammatory diseases <a href="https://pubmed.ncbi.nlm.nih.gov/32542149/">occur in females</a>. Diseases more common in women include multiple sclerosis, <a href="https://www.nature.com/articles/nri2815">rheumatoid arthritis</a>, lupus, Sjogren’s syndrome, and <a href="https://www.nature.com/articles/nri.2016.90">thyroid disorders</a> such as Graves disease.</p>
<p>In these diseases, the immune system is continuously fighting against what it sees as a foreign agent. However, often this perceived threat is not a foreign agent, but cells or tissues from the host. This leads to tissue damage, pain and immobility.</p>
<p>Women are also prone to chronic inflammation following infection. For example, after infections with <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5818468/">Epstein Barr virus</a> or <a href="https://www.liebertpub.com/doi/10.1089/jwh.2008.1193">Lyme disease</a>, they may go on to develop <a href="https://www.nhs.uk/conditions/chronic-fatigue-syndrome-cfs/">chronic fatigue syndrome</a>, another condition that affects more women than men.</p>
<p>This is one possible explanation for the heightened risk among <a href="https://www.frontiersin.org/articles/10.3389/fresc.2023.1122673/full">pre-menopausal women</a> of developing long COVID following infection with SARS-CoV-2, the virus that causes COVID. </p>
<p>Research has also revealed the presence of auto-antibodies (antibodies that attack the host) in patients with long COVID, suggesting it might be an <a href="https://www.sciencedirect.com/science/article/pii/S1568997221000550">autoimmune disease</a>. As women are more susceptible to autoimmune conditions, this could potentially explain the sex bias seen. </p>
<p>However, the exact causes of long COVID, and the reason women may be at greater risk, are yet to be defined. </p>
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<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/long-covid-female-sex-older-age-and-existing-health-problems-increase-risk-new-research-185911">Long COVID: female sex, older age and existing health problems increase risk – new research</a>
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<hr>
<p>This paints a bleak picture, but it’s not all bad news. Women typically mount <a href="https://pubmed.ncbi.nlm.nih.gov/24966191/">better vaccine responses</a> to several common infections (for example, influenza, measles, mumps, rubella, hepatitis A and B), producing higher antibody levels than men. </p>
<p>One study showed that women vaccinated with half a dose of flu vaccine produced the same amount of antibodies compared to men vaccinated with <a href="https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/773453">a full dose</a>. </p>
<p>However, these responses <a href="https://www.nature.com/articles/nri.2016.90">decline as women age</a>, and particularly <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3954964/">after menopause</a>. </p>
<p>All of this shows it’s vital to consider sex when designing studies examining the immune system and treating patients with immune-related diseases.</p><img src="https://counter.theconversation.com/content/208802/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Helen McGettrick receives funding from the Medical Research Council, Biotechnology and Biological Sciences Research Council, Wellcome Trust, F Hoffmann-La Roche Ag, Versus Arthritis, Dompè Pharmaceuticals Ltd, Novartis, Chernajovsky Foundation, British Heart Foundation, Pfizer. </span></em></p><p class="fine-print"><em><span>Asif Iqbal receives funding from, Wellcome Trust, F Hoffmann-La Roche, Chernajovsky Foundation, British Heart Foundation. </span></em></p>Women are more likely to develop chronic diseases driven by the immune system.Helen McGettrick, Reader in Inflammation and Vascular Biology, University of BirminghamAsif Iqbal, Associate Professor in Inflammation Biology, University of BirminghamLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/2078362023-07-13T11:46:33Z2023-07-13T11:46:33ZFungal infections in the brain aren’t just the stuff of movies – Africa grapples with a deadly epidemic<figure><img src="https://images.theconversation.com/files/532417/original/file-20230616-19-tunqcw.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">The fungus Aspergillus fumigatus. This fungus can cause a number of disorders in people with compromised immune function or other lung diseases.</span> <span class="attribution"><span class="source">Kateryna Kon/Science Photo Library/GettyImages</span></span></figcaption></figure><p>In the 2023 American post-apocalyptic drama television series <a href="https://www.hbo.com/the-last-of-us">The Last of Us</a>, humans are plunged towards extinction as a fungal infection of the brain zombie-fies most of the species. This may seem far-fetched but fungi can, and do, infect human brains.</p>
<p>Fungi are present everywhere in our environment: in the air, in the soil, in decaying plant material, on our skin, and even in the gut as part of our natural flora.</p>
<p>Microscopic, disease-causing fungi can invade various parts of the body, leading to a range of symptoms and health problems. In fact, fungal infections contribute to <a href="https://doi.org/10.3390%2Fjof7050367">about 1.5 million deaths</a> every year. </p>
<p>I am a neurobiologist who has been studying fungal infections of the brain for 10 years. I was part of a team that recently <a href="https://doi.org/10.1111/pim.12953">published a review</a> discussing the emergence, and re-emergence, of fungal infections in Africa, especially in sub-Saharan Africa. We conclude that Africa is suffering from a silent, but costly, epidemic of fungal infections. We found that the emergence of deadly fungal infections in the region is primarily driven by a high burden of HIV infections, lack of access to quality healthcare, and unavailability of effective antifungal drugs.</p>
<h2>What are fungal infections?</h2>
<p>For the greater part of the history of humankind, fungal infections were never a threat to human health. This is mainly because most fungi cannot survive the warm human body temperature of 37°C. However, climate change and other environmental pressures <a href="https://doi.org/10.1016/j.joclim.2022.100156">have led</a> to the emergence of species of fungi that are capable of surviving at human body temperatures. </p>
<p>Even then, our immune systems are quite capable of fighting against fungal infections. For instance, our bodies can create localised acidic environments, limit micronutrient availability and release antimicrobial agents. </p>
<p>However, when the immune system is weakened, fungi are able to evade the body’s defences and avoid detection. They can generate bioactive agents which help them evade or adjust to the host immune response. Some adapt to survive in hostile, low-nutrient and low-oxygen environments. </p>
<p>Immunocompromised people are at risk of developing serious or life-threatening fungal diseases. Africa accounts for <a href="https://www.unaids.org/sites/default/files/media_asset/UNAIDS_FactSheet_en.pdf">67%</a> of the global burden of HIV, and opportunistic fungal diseases <a href="https://doi.org/10.1111/pim.12953">are on the rise</a>.</p>
<h2>Some examples</h2>
<p>One example of opportunistic fungal diseases is <a href="https://www.ncbi.nlm.nih.gov/books/NBK525986/">cryptococcal meningitis</a>, which emerged with the HIV pandemic in the late 1980s. Today, sub-Saharan Africa contributes about <a href="https://doi.org/10.1016/s1473-3099(17)30243-8">73%</a> of all global cases and deaths resulting from the disease. Cryptococcal meningitis is caused by the fungus <em>Cryptococcus neoformans</em>, which is found in soil and bird droppings. Infection by the fungus occurs when someone inhales fungal spores. It first leads to the development of a lung infection and later a fatal brain infection. Cryptococcal meningitis is a leading cause of adult meningitis in sub-Saharan Africa and it’s associated with <a href="https://doi.org/10.1016/S1473-3099(22)00499-6">almost 20%</a> of all AIDS-related deaths. </p>
<p>Effective treatments for cryptococcal meningitis are unaffordable and inaccessible for most affected people. Costs <a href="https://doi.org/10.1093/cid/ciy971">range between</a> US$1,400 and US$2,500 per patient for a full two-week antifungal treatment course. </p>
<p>The development of cheaper drugs has been hindered by a limited understanding of how the fungus causes such extreme damage in the brain. </p>
<p>Another example of an HIV-related opportunistic fungal disease is pneumocystis jirovecii pneumonia. It’s caused by a ubiquitous, airborne fungus <em>Pneumocystis jirovecii</em>, which is passed on from person to person. Pneumocystis hardly causes trouble in people with healthy immune systems, but they act as reservoirs and pass the infection to those with poor immune systems, who may develop serious symptoms including fever, a dry cough and trouble with breathing. Pneumocystis jirovecii pneumonia occurs in <a href="https://doi.org/10.1186/s12879-016-1809-3">15%-20%</a> of HIV patients who present with respiratory problems. </p>
<p>The diagnosis of pneumocystis jiroveci pneumonia is expensive and requires a well-equipped laboratory. In Africa’s poor urban and rural healthcare facilities this will be a challenge. The fungus, <em>P. jirovecii</em>, is also extremely difficult to culture, which limits diagnosis and research. </p>
<h2>Growing burden</h2>
<p>In our review, <a href="https://doi.org/10.1111/pim.12953">we found</a> various factors driving the emergence and reemergence of fungal threats. They include climate change, the spread of immunosuppressive diseases, medical advances such as organ transplants (the immune system is suppressed to minimise rejection), the use of immunosuppressants to manage inflammatory diseases, and the use of antibiotics. </p>
<p>While these factors are not unique to Africa, the burden of fungal diseases and the number of people who succumb to them is much greater. </p>
<p>The COVID pandemic seems to have made the global fungal burden worse. For instance, <a href="https://doi.org/10.1016/j.gr.2021.12.016">recent studies</a> have <a href="https://doi.org/10.4103%2Fijd.ijd_17_22">shown</a> that people who were infected with COVID and have recovered are vulnerable to infection with a fungus called mucormycosis, also known as the black fungus. COVID-induced lung damage, high blood sugar, and the steroids often used to treat it are all predisposing factors to black fungus infection. With a reduced capacity to clear fungal spores and a reduced immune response, thanks to the steroids, the fungus can gain entry and infect the sinuses and facial bones, eventually moving to the brain. </p>
<h2>But don’t we have antifungal drugs?</h2>
<p>Most of the population affected by fungal infections live in rural or poor urban settlements. </p>
<p>With poorly funded and overburdened healthcare systems, many African countries are not well prepared to deal with fungal infections. Additionally, some of the WHO-recommended antifungal drugs – such as flucytosine – are <a href="https://gaffi.org/antifungal-drug-maps/">unavailable</a> in most African countries. Ineffective and even rather toxic drugs are sometimes used instead. </p>
<p>The emergence of drug-resistant fungal strains is also a growing threat. Of great concern is the rise in multi-drug resistant Candida species, <a href="https://doi.org/10.1007/s11908-019-0702-9">azole-resistant Aspergillus</a> species and clinically resistant <a href="https://doi.org/10.1007/978-1-60327-595-8_20">Cryptococcus</a>. </p>
<h2>Management strategies</h2>
<p>Fungal threats are adding pressure to overburdened health systems with a limited arsenal of treatment options. </p>
<p>Healthcare professionals, scientific researchers, policymakers and governments must address the gaps in the diagnosis and management of fungal infections. This will help to improve capacity to deal with them.</p><img src="https://counter.theconversation.com/content/207836/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Rachael Dangarembizi is a scientific researcher in the field of neuroscience and medical mycology and her research is funded by several funding bodies including the Gabriel Foundation and the UK Medical Research Council. </span></em></p>Africa is suffering from a silent, but costly, epidemic of fungal infections.Rachael Dangarembizi, Neuroinfections Researcher, Neuroscience Institute, University of Cape TownLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/2069242023-06-05T15:01:08Z2023-06-05T15:01:08ZSeveral Down syndrome features may be linked to a hyperactive antiviral immune response – new research<figure><img src="https://images.theconversation.com/files/529898/original/file-20230603-15-so1fli.jpg?ixlib=rb-1.1.0&rect=0%2C0%2C3679%2C2647&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Addressing the increased risks of certain diseases among those with Down syndrome could help improve their quality of life.</span> <span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/photo/boy-with-down-syndrome-playing-outdoors-in-garden-royalty-free-image/1271658791">Halfpoint Images/Moment via Getty Images</a></span></figcaption></figure><p>People with <a href="https://www.globaldownsyndrome.org/about-down-syndrome/facts-about-down-syndrome/">Down syndrome</a>, or trisomy 21, a genetic condition caused by an extra copy of human chromosome 21, experienced a remarkable increase in life expectancy during the 20th century. In the early 1900s, less than 20% of newborns with Down syndrome <a href="https://doi.org/10.1038/gim.2016.127">survived past age 5</a>. In the U.S. today, more than 90% of babies with this condition <a href="https://doi.org/10.1038/gim.2016.127">live past age 10</a> and have a life expectancy of <a href="https://doi.org/10.1001/jamanetworkopen.2022.12910">nearly 60 years</a>. These increases were <a href="https://doi.org/10.1016%2FS0074-7750(10)39004-5">likely fueled</a> by greater inclusion in general society, the discontinuation of institutionalization in psychiatric facilities and better medical care.</p>
<p>Despite these advances, people with trisomy 21 experience an increased risk of many <a href="https://doi.org/10.1038/s41572-019-0143-7">co-occurring conditions</a>, such as congenital heart defects, autoimmune conditions, autism spectrum disorders and Alzheimer’s disease. On the other hand, people with Down syndrome tend to have <a href="https://doi.org/10.17294/2330-0698.1824">lower levels of hypertension</a> and <a href="https://doi.org/10.1038/gim.2016.23">certain types of cancers</a>.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/529897/original/file-20230603-25-nrpa24.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="Karyotype of Down syndrome, with a circle around three copies of chromosome 21" src="https://images.theconversation.com/files/529897/original/file-20230603-25-nrpa24.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/529897/original/file-20230603-25-nrpa24.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=480&fit=crop&dpr=1 600w, https://images.theconversation.com/files/529897/original/file-20230603-25-nrpa24.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=480&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/529897/original/file-20230603-25-nrpa24.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=480&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/529897/original/file-20230603-25-nrpa24.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=603&fit=crop&dpr=1 754w, https://images.theconversation.com/files/529897/original/file-20230603-25-nrpa24.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=603&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/529897/original/file-20230603-25-nrpa24.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=603&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Down syndrome is also called trisomy 21 because those with the condition have three copies of chromosome 21.</span>
<span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/illustration/downs-syndrome-karyotype-illustration-royalty-free-illustration/685025123">Kateryna Kon/Science Photo Library via Getty Images</a></span>
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<p>Understanding how an extra chromosome 21 causes these risks and resiliencies could advance collective understanding of major medical conditions that also affect the general population. For example, the <a href="https://doi.org/10.1038/s41582-018-0132-6">increased risk of Alzheimer’s disease</a> among adults with Down syndrome can be explained in part by the presence of a gene on chromosome 21 that leads to excess production of the beta-amyloid proteins and plaques characteristic of Alzheimer’s.</p>
<p>In our newly published research, my research team <a href="https://scholar.google.com/citations?user=6gRbVeAAAAAJ&hl=en">and I</a> found that <a href="https://www.nature.com/articles/s41588-023-01399-7">genes involved in controlling the immune system</a> are critical to the development of multiple hallmarks of Down syndrome. Our findings contribute to a growing body of research on the immune system’s important role in the appearance and severity of some of the negative health effects of trisomy 21, supporting the idea that restoring immune balance could help improve the quality of life of people with the condition.</p>
<h2>When too much of a good thing is bad</h2>
<p>The genes we identified, which encode what are called <a href="https://doi.org/10.1038%2Ficb.2012.9">interferon receptors</a>, are an important part of the immune system’s antiviral defense. These genes enable our cells to recognize a set of proteins called interferons, which virus-infected cells produce to alert the yet uninfected cells around them about the presence of a virus during an infection.</p>
<p>While interferons do trigger a beneficial immune response against viral infections, chronic interferon hyperactivity could have detrimental effects. Too much interferon signaling is known to be harmful in medical conditions such as <a href="http://dx.doi.org/10.1136/lupus-2018-000270">systemic lupus erythematosus</a>, a group of genetic disorders known as <a href="https://doi.org/10.1038/s41577-021-00633-9">interferonopathies</a> and <a href="https://doi.org/10.1038/s41577-020-00429-3">severe COVID-19</a>.</p>
<figure class="align-right zoomable">
<a href="https://images.theconversation.com/files/529899/original/file-20230603-17-pq5zrq.png?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="3D model of human interferon-beta structure" src="https://images.theconversation.com/files/529899/original/file-20230603-17-pq5zrq.png?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/529899/original/file-20230603-17-pq5zrq.png?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=418&fit=crop&dpr=1 600w, https://images.theconversation.com/files/529899/original/file-20230603-17-pq5zrq.png?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=418&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/529899/original/file-20230603-17-pq5zrq.png?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=418&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/529899/original/file-20230603-17-pq5zrq.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=526&fit=crop&dpr=1 754w, https://images.theconversation.com/files/529899/original/file-20230603-17-pq5zrq.png?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=526&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/529899/original/file-20230603-17-pq5zrq.png?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=526&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Interferons are involved in antiviral immune responses.</span>
<span class="attribution"><a class="source" href="https://commons.wikimedia.org/wiki/File:1AU1_Human_Interferon-Beta05.png">Nevit Dilmen/Wikimedia Commons</a>, <a class="license" href="http://creativecommons.org/licenses/by-sa/4.0/">CC BY-SA</a></span>
</figcaption>
</figure>
<p>Notably, four of the six human interferon receptor genes are <a href="https://doi.org/10.1038%2Ficb.2012.9">located on chromosome 21</a>. Most people have only two copies of each chromosome and so would have only two copies of these genes. Because people with Down syndrome have three copies of chromosome 21, they also have three copies of the interferon receptor genes on it. This contributes to the <a href="https://doi.org/10.7554/eLife.16220">overproduction of interferon receptors</a> seen in those with Down syndrome.</p>
<p>Our team wanted to know whether this <a href="https://www.nature.com/articles/s41588-023-01399-7">extra copy of interferon receptor genes</a>, compared with the roughly 200 other genes located on chromosome 21, contribute to features of Down syndrome. To do this, we used a mouse model of Down syndrome. In this mouse model, a large region of its genome that is equivalent to a large portion of human chromosome 21 is triplicated to reproduce many features of Down syndrome.</p>
<p>Using <a href="https://theconversation.com/human-genome-editing-offers-tantalizing-possibilities-but-without-clear-guidelines-many-ethical-questions-still-remain-200983">CRISPR gene editing</a> technology, we reduced the number of interferon receptor genes from three to the typical two, leaving all other triplicated genes intact. We found that <a href="https://www.nature.com/articles/s41588-023-01399-7">correcting the number of interferon receptor genes</a> significantly reduced abnormal gene expression patterns across multiple tissue types, both during embryonic development and in adult mice. These mice also had more regulated immune responses, normal heart development, reduced developmental delays, improved performance on memory and learning tasks and even a more typical skull and facial morphology.</p>
<p>Overall, our findings suggest that the tripling of interferon receptor genes may cause a number of key traits of Down syndrome.</p>
<h2>Therapeutic implications and future directions</h2>
<p>Our research indicates that many, though not all, aspects of Down syndrome may be associated with hyperactivity of the immune system’s interferon response. It also supports the possibility of using drugs that attenuate this response to treat some of the negative health effects of trisomy 21.</p>
<p>Our team is currently leading two clinical trials to test the safety and efficacy of one such drug, <a href="https://www.uptodate.com/contents/tofacitinib-drug-information">tofacitinib (Xeljanz)</a>. This drug belongs to a class of drugs known as JAK inhibitors used to treat autoinflammatory conditions. One trial <a href="https://clinicaltrials.gov/ct2/show/NCT04246372">focuses on autoimmune skin conditions</a> more common in Down syndrome. The second trial <a href="https://clinicaltrials.gov/ct2/show/NCT05662228">focuses on Down syndrome regression disorder</a>, or DSRD, a rare but devastating <a href="https://doi.org/10.3389%2Ffneur.2022.940175">neurological condition</a> that can result in loss of speech, sleep disruptions, difficulty moving and hallucinations. There is evidence that suggests that a subset of DSRD cases may be caused by <a href="https://doi.org/10.1186/s11689-022-09446-w">immune dysregulation affecting the brain</a>.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/529900/original/file-20230603-27-v9th5q.png?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="Person with Down syndrome holding a potted plant in a nursery" src="https://images.theconversation.com/files/529900/original/file-20230603-27-v9th5q.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/529900/original/file-20230603-27-v9th5q.png?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/529900/original/file-20230603-27-v9th5q.png?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/529900/original/file-20230603-27-v9th5q.png?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/529900/original/file-20230603-27-v9th5q.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/529900/original/file-20230603-27-v9th5q.png?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/529900/original/file-20230603-27-v9th5q.png?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=503&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Treating the common health risks that occur with Down syndrome could help improve quality of life.</span>
<span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/photo/portrait-of-happy-confident-florist-in-flower-shop-royalty-free-image/1327764759">Flashpop/DigitalVision via Getty Images</a></span>
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<p>Our study findings also support further investigation into the effects of interferon hyperactivity on fetal development more generally. Two of the key traits of Down syndrome that we found were affected by the tripling of interferon receptors – congenital heart disease and skull and facial shape – develop in utero.</p>
<p>Though our research shows promise on the potential of JAK inhibitors and other drugs that modulate the immune system to improve health outcomes in Down syndrome, more research in people is needed to determine their safety and efficacy.</p><img src="https://counter.theconversation.com/content/206924/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Joaquin Espinosa receives funding from the National Institutes of Health, the Global Down Syndrome Foundation, and the Anna and John J. Sie Foundation. Dr. Espinosa has provided consulting services to Elli Lily and Co. and Gilead Sciences Inc. and currently serves in the advisory board of Perha Pharmaceuticals.</span></em></p>People with Down syndrome have an extra chromosome 21. Understanding the effects of those triplicated genes could help improve the health of those with Down syndrome and other medical conditions.Joaquin Espinosa, Professor of Pharmacology, University of Colorado Anschutz Medical CampusLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/2059042023-05-19T15:29:20Z2023-05-19T15:29:20ZMultiple sclerosis: new evidence for the role of glandular fever virus<figure><img src="https://images.theconversation.com/files/527226/original/file-20230519-27-bsi0zs.jpg?ixlib=rb-1.1.0&rect=0%2C0%2C8986%2C5982&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">
</span> <span class="attribution"><a class="source" href="https://www.shutterstock.com/image-illustration/epsteinbarr-virus-ebv-herpes-which-causes-497941504">Kateryna Kon/Shutterstock</a></span></figcaption></figure><p>An estimated <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7720355/">2.8 million people</a> around the world have <a href="https://www.thelancet.com/article/S1474-4422(17)30470-2/fulltext">multiple sclerosis</a> (MS), an autoimmune disease in which the immune system damages the brain and spinal cord.</p>
<p>Symptoms include fatigue, vision disturbance, problems with mobility and balance and cognitive dysfunction. Many people who develop MS experience symptoms followed by a period of recovery, but over time the disease can progress to permanent disability. </p>
<p>The exact causes of MS are unknown. But for decades scientists have suggested a link between MS and <a href="https://www.nature.com/articles/s41579-022-00770-5">Epstein-Barr virus</a> (EBV). This is an infection which, when contracted in childhood, generally doesn’t cause symptoms. However, infection in adolescence can lead to glandular fever, also called the “kissing disease” or infectious mononucleosis (“mono”). </p>
<p>A <a href="https://www.science.org/doi/10.1126/science.abj8222">2022 study</a> confirmed that people with MS have almost always been infected with EBV previously (generally the infection occurs <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3089959/">several years</a> before MS emerges).</p>
<p>But researchers are still debating exactly how this common virus could cause MS in certain people. Our <a href="https://www.science.org/doi/10.1126/sciadv.adg3032">new research</a> offers some clues.</p>
<h2>A bit of background</h2>
<p>When your body encounters an infection it generates an immune response so that next time you are exposed you will already have some protection from illness.</p>
<p>Normally, in healthy people, immune cells called T cells and B cells are generated against a single target such as one part of a virus or bacteria, and their job is to fight infection. B cells <a href="https://www.mdanderson.org/cancerwise/t-cells--b-cells-and-the-immune-system.h00-159465579.html">produce antibodies</a> which bind to and destroy invading viruses or bacteria.</p>
<p><a href="https://www.healthline.com/health/autoimmune-disorders">Autoimmune diseases</a> – of which MS is one – occur when the body’s immune system damages itself by mistake. This can be caused by a phenomenon called <a href="https://pubmed.ncbi.nlm.nih.gov/30509385/">molecular mimicry</a>, which generally happens when immune cells, originally generated to fight infection, instead attack proteins in the body of a similar shape. </p>
<p>This causes a variety of symptoms and diseases depending on which part of the body the immune system is targeting. In MS, because the brain and spinal cord are affected, the condition leads to a range of neurological symptoms.</p>
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<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/childhood-obesity-could-increase-the-risk-of-multiple-sclerosis-in-later-life-144975">Childhood obesity could increase the risk of multiple sclerosis in later life</a>
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<h2>Misdirected immunity</h2>
<p>To understand how this process plays out in MS patients in greater detail, my colleagues and I studied blood samples from more than <a href="https://www.science.org/doi/10.1126/sciadv.adg3032">700 people with MS</a> and a similar number without the disease (a control group).</p>
<p>We found that antibodies that bind to a protein from EBV, called EBNA1, were increased in MS patients. This was not surprising – previous research has shown antibodies against EBNA1 <a href="https://pubmed.ncbi.nlm.nih.gov/21685232/">are higher</a> in people with MS. </p>
<p>But their role in disease has remained something of a question mark. Our study found that these antibodies generated in response to EBNA1, rather than fighting EBV infection, instead can target a similar-looking protein found in areas of the brain that become inflamed in MS, called alpha crystallin B, or Cryab.</p>
<p>Cryab plays a crucial role in protecting against the effects of inflammation, and so if antibodies are mistakenly targeting this protein, this could go some way to explaining the symptoms seen in MS.</p>
<figure class="align-center ">
<img alt="A woman sits on a bench in a park holding a walking cane." src="https://images.theconversation.com/files/527227/original/file-20230519-21-ris0qb.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/527227/original/file-20230519-21-ris0qb.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=399&fit=crop&dpr=1 600w, https://images.theconversation.com/files/527227/original/file-20230519-21-ris0qb.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=399&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/527227/original/file-20230519-21-ris0qb.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=399&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/527227/original/file-20230519-21-ris0qb.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=502&fit=crop&dpr=1 754w, https://images.theconversation.com/files/527227/original/file-20230519-21-ris0qb.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=502&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/527227/original/file-20230519-21-ris0qb.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=502&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">Around 2.8 million people globally are currently living with MS.</span>
<span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/portrait-happy-senior-woman-summer-park-2212910945">Hryshchyshen Serhii/Shutterstock</a></span>
</figcaption>
</figure>
<p>We found that that these Cryab antibodies were present in up to 23% of MS patients and only 7% of controls, suggesting this process could be involved in either the triggering or progression of MS disease in up to one-quarter of patients.</p>
<p>These findings are intriguing but show there is high variation between people with the disease, and suggest that there may be several slightly different ways to develop MS.</p>
<p>Previous studies have shown that EBNA1 antibodies can also bind to other proteins in the body such as <a href="https://www.pnas.org/doi/10.1073/pnas.1902623116">anoctamin-2</a> and <a href="https://www.nature.com/articles/s41586-022-04432-7">GlialCAM</a>, similarly more common in people with MS.</p>
<h2>What about T cells?</h2>
<p>While EBV antibodies are thought to be involved in MS, they’re unlikely to fully explain why some people develop disease. Researchers believe <a href="https://www.britannica.com/science/T-cell">T cells</a> – soldiers of the immune system which work alongside antibodies – might be involved as well. </p>
<p>So we also investigated the role of T cells, and found that they can likely cross-react to EBNA1 and Cryab in a similar way.</p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/link-between-epstein-barr-virus-and-multiple-sclerosis-is-a-crucial-discovery-for-people-living-with-ms-175908">Link between Epstein-Barr virus and multiple sclerosis is a crucial discovery for people living with MS</a>
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</em>
</p>
<hr>
<p>Despite these advances in our understanding of how the immune response to EBV may be involved in MS, we still don’t fully understand what happens in early disease or what drives progression. </p>
<p>We are now expanding our research to understand how T cells fight EBV infection and how these cells may damage the central nervous system. It’s likely that there may also be other proteins which which can be targeted by EBV immune responses in MS, and our research is exploring this possibility. </p>
<p>While available therapies are highly effective at reducing <a href="https://pubmed.ncbi.nlm.nih.gov/16510744/">relapse rates</a>, there are currently no treatments which ultimately prevent progression of disease. Hopefully, greater understanding of the disease will pave the way for development of personalised therapies with the potential to cure MS.</p><img src="https://counter.theconversation.com/content/205904/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Olivia Thomas does not work for, consult, own shares in or receive funding from any company or organisation that would benefit from this article, and has disclosed no relevant affiliations beyond their academic appointment.</span></em></p>Recent research has shown there’s a link between multiple sclerosis and Epstein-Barr virus. A new study brings us closer to understanding the nature of this connection.Olivia Thomas, Postdoctoral Researcher, Department of Clinical Neuroscience, Karolinska InstitutetLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/2033052023-04-14T16:00:19Z2023-04-14T16:00:19ZEndometriosis: how the condition may be linked to the immune system<figure><img src="https://images.theconversation.com/files/521036/original/file-20230414-20-758qyg.jpg?ixlib=rb-1.1.0&rect=0%2C0%2C6944%2C3783&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Endometriosis can cause a range of painful symptoms.</span> <span class="attribution"><a class="source" href="https://www.shutterstock.com/image-illustration/endometriosis-disease-anatomy-concept-female-infertility-2145269393">Lightspring/ Shutterstock</a></span></figcaption></figure><p>Endometriosis is a debilitating condition which affects <a href="https://www.who.int/news-room/fact-sheets/detail/endometriosis">10% of women worldwide</a>. The condition can have a serious affect on a person’s quality of life, often causing a range of symptoms including chronic pain, fatigue and pain during sex.</p>
<p>Despite how common endometriosis is, most women wait on average <a href="https://www.endometriosis-uk.org/sites/endometriosis-uk.org/files/files/Endometriosis%20APPG%20Report%20Oct%202020.pdf">7.5 years</a> for a diagnosis in the UK. Not only does this mean many years without treatment, it also puts them at risk of even greater health problems. Untreated endometriosis can lead to <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3825702/">organ damage</a> (including the uterus and bowels) and <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2941592/">infertility</a>.</p>
<p>There’s currently no cure for endometriosis. This may be due to how complex endometriosis is, affecting many different parts of the body – meaning researchers still don’t fully understand all the causes of the disease. </p>
<p>In the last few years, studies have found that the immune system is also affected by endometriosis. It’s still unclear whether the immune system causes endometriosis or is merely affected by it. But exploring this link could eventually lead to better targeted treatment for the condition.</p>
<h2>Inflammation and immunity</h2>
<p>To understand how our immune system and endometriosis are connected, it’s first important to understand an immune system process called inflammation.</p>
<p>Inflammation is a key feature of how our immune system works. When the body encounters a harmful pathogen (such as a virus or bacteria), our immune system is triggered. The body then secretes special proteins called cytokines, which tell our immune cells what to do.</p>
<p>The symptoms you experience as a result of inflammation will depend on the reason these cells have been mobilised. For example, if your inflammation is caused by a cut to your finger, you may find the area around the cut becomes hot, red and swollen as the immune system works to combat pathogens and repair the damage. If inflammation is caused by a virus, you might experience flu-like symptoms – such as a fever.</p>
<p>For the most part, inflammation is a short-term process. But sometimes the immune system gets things wrong, and your body continues to send inflammatory cells and cytokines even when there’s no threat. Autoimmune diseases such as rheumatoid arthritis are an example of this, where the body’s immune system continues to attack, leading to long-term inflammation in the joints.</p>
<figure class="align-center ">
<img alt="A digital image of a group of natural killer cells attacking a COVID cell." src="https://images.theconversation.com/files/521039/original/file-20230414-26-pffr0y.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/521039/original/file-20230414-26-pffr0y.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=338&fit=crop&dpr=1 600w, https://images.theconversation.com/files/521039/original/file-20230414-26-pffr0y.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=338&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/521039/original/file-20230414-26-pffr0y.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=338&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/521039/original/file-20230414-26-pffr0y.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=424&fit=crop&dpr=1 754w, https://images.theconversation.com/files/521039/original/file-20230414-26-pffr0y.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=424&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/521039/original/file-20230414-26-pffr0y.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=424&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
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<span class="caption">Natural killer cells are one type of immune cell which helps protect the body from harm.</span>
<span class="attribution"><a class="source" href="https://www.shutterstock.com/image-illustration/3d-render-illustration-natural-killer-body-1794879802">Numstocker/ Shutterstock</a></span>
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<p>Inflammation is also a normal feature of the menstrual cycle.</p>
<p>The normal menstrual cycle consists of two phases: the follicular phase (from the first day of the period until ovulation) and the luteal phase (from ovulation until your period starts). Most inflammation during the menstrual cycle happens in the uterus, but changes may also occur <a href="https://pubmed.ncbi.nlm.nih.gov/36883215/">throughout the body</a>.</p>
<p>During the follicular phase, there are increased levels of oestrogen circulating in the body. Oestrogen stimulates the lining of the uterus to thicken in preparation for a fertilised embryo.</p>
<p>But some immune cells have specific receptors which recognise oestrogen, causing them to initiate an <a href="https://pubmed.ncbi.nlm.nih.gov/22155200">immune response</a>. This readies the body to fight off any foreign invaders so it’s healthy for pregnancy, should fertilisation occur. As such, women will be less susceptible to infections during the follicular phase. However, women with autoimmune diseases may experience more symptoms at this stage.</p>
<p>But in order not to reject a fertilised egg, the immune system is then suppressed during the luteal phase – which may subsequently increase risk of infection, and cause relief from some autoimmune symptoms.</p>
<h2>Endometriosis and immunity</h2>
<p>Research has observed multiple immune system changes in people with endometriosis.</p>
<p>One study found patients with endometriosis had elevated inflammation levels (specifically higher levels of <a href="https://pubmed.ncbi.nlm.nih.gov/30367890/">cytokines</a>). Research has also shown that people with endometriosis have disturbed immune cell function – namely a specific type of immune cell called natural killer cells. </p>
<p>These have a vital role in fighting viruses and tumours, but research shows they <a href="https://www.frontiersin.org/articles/10.3389/fimmu.2021.711231/full">function more poorly</a> in people with endometriosis. The uterine lining in patients with endometriosis is also shown to <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1858106/">produce excess molecules</a> called chemokines that attract other immune cells, worsening inflammation. </p>
<p>Again, it’s still not certain whether altered immune function causes endometriosis or is merely a symptom of the disease. But immune system dysfunction may explain why there’s a suspected association between people with endometriosis and <a href="https://pubmed.ncbi.nlm.nih.gov/31260048/">autoimmune disorders</a> such as lupus, rheumatoid arthritis and inflammatory bowel disease. </p>
<p>Elevated inflammation levels also mean that women with endometriosis may be more likely to experience worse symptoms during infections. For example, research has found that when patients with endometriosis catch COVID-19, their <a href="https://bmcwomenshealth.biomedcentral.com/articles/10.1186/s12905-021-01270-z">symptoms appear to be worse</a> than people who don’t have the condition. </p>
<p>COVID-19 may also <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9657778/pdf/ijms-23-12951.pdf">worsen endometriosis symptoms</a> – particularly pelvic pain, depression, fatigue and gastrointestinal issues. A <a href="https://pubmed.ncbi.nlm.nih.gov/36972892/">recent study</a> has also found that women with endometriosis were 22% more likely to suffer long COVID – and their long COVID symptoms may last longer.</p>
<p>While it’s currently not known how precisely the immune system is linked with endometriosis (and whether it causes the disease), working to further understand this relationship could be key in helping develop better treatments – or possibly even a cure – for endometriosis.</p>
<p>Research into this disease is still <a href="https://pubmed.ncbi.nlm.nih.gov/35620300/">severely under-funded</a>, and the time to diagnosis is far beyond what would be expected from other chronic conditions – such as asthma or diabetes. It’s clear that greater priority needs to be placed into researching endometriosis and its causes to help provide new insights and better treatment for the millions of women affected.</p><img src="https://counter.theconversation.com/content/203305/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>April Rees does not work for, consult, own shares in or receive funding from any company or organisation that would benefit from this article, and has disclosed no relevant affiliations beyond their academic appointment.</span></em></p>Further exploring this connection could potentially lead to better treatment of the condition.April Rees, Biochemistry Tutor, Swansea UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/2001992023-03-01T13:25:49Z2023-03-01T13:25:49ZBile acids and gut microbes could potentially treat multiple sclerosis, according to new research in mice<figure><img src="https://images.theconversation.com/files/512506/original/file-20230227-716-vd1jv0.jpg?ixlib=rb-1.1.0&rect=0%2C0%2C2309%2C1299&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Multiple sclerosis involves the immune system attacking the protective myelin sheath of neurons.</span> <span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/photo/neuron-tem-view-royalty-free-image/1204279188">koto_feja/iStock via Getty Images Plus</a></span></figcaption></figure><p><a href="https://www.mayoclinic.org/diseases-conditions/multiple-sclerosis/symptoms-causes/syc-20350269">Multiple sclerosis</a> is characterized by an immune system gone haywire. A patient’s immune system starts treating the protective coating of the nerves – called <a href="https://my.clevelandclinic.org/health/body/22974-myelin-sheath">myelin</a> – as dangerous. The subsequent nerve damage can cause a variety of symptoms, including muscle weakness, pain and vision loss. MS currently has no cure, and doctors still don’t completely understand what causes it.</p>
<p>While there is a genetic component to MS, <a href="http://doi.org/10.1101/cshperspect.a028944">environmental factors</a> also play a big role in determining whether someone will develop the disease. <a href="https://doi.org/10.1016/j.intimp.2020.107024">Recent evidence</a> suggests that what’s in your digestive tract may also be a meaningful contributor to disease risk. </p>
<p>My colleagues <a href="https://scholar.google.com/citations?user=X8XcETAAAAAJ&hl=en">and I</a> at the University of Virginia are working to understand the two-way communication between the human body and the bacteria that live in its digestive system. In our <a href="https://doi.org/10.1371/journal.pbio.3002000">recently published research</a>, we found that bile acid in the intestines could be harnessed to protect people at high risk of MS from developing the disease, offering a new avenue for drug development.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/512502/original/file-20230227-155-mhfk7f.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="Diagram comparing healthy nerve and nerve affected by multiple sclerosis" src="https://images.theconversation.com/files/512502/original/file-20230227-155-mhfk7f.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/512502/original/file-20230227-155-mhfk7f.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=356&fit=crop&dpr=1 600w, https://images.theconversation.com/files/512502/original/file-20230227-155-mhfk7f.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=356&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/512502/original/file-20230227-155-mhfk7f.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=356&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/512502/original/file-20230227-155-mhfk7f.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=447&fit=crop&dpr=1 754w, https://images.theconversation.com/files/512502/original/file-20230227-155-mhfk7f.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=447&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/512502/original/file-20230227-155-mhfk7f.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=447&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Multiple sclerosis results when the immune system attacks the protective myelin sheath of neurons.</span>
<span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/illustration/multiple-sclerosis-royalty-free-illustration/530457339">ttsz/iStock via Getty Images Plus</a></span>
</figcaption>
</figure>
<h2>The gut microbiome and autoimmunity</h2>
<p><a href="https://www.hsph.harvard.edu/nutritionsource/microbiome/">Trillions of bacteria</a> live in the human gut. They help the body with everything from digesting food to preventing the overgrowth of infectious and dangerous bacteria. They also <a href="https://www.youtube.com/watch?v=gnZEge78_78&t=151s">“educate” the immune system</a> to recognize what is dangerous and what is not. If this process is disturbed, the immune system may become overactive and start to treat natural parts of the body as dangerous. This is called autoimmunity.</p>
<p>Scientists believe that one way bacteria and the immune system communicate with each other is through the <a href="https://doi.org/10.1038/s41423-020-00585-5">aryl hydrocarbon receptor, or AHR</a>, which resides in most cells of the body. This protein acts like an emergency call center – when it encounters certain chemicals, it will identify the appropriate response and send a signal to the cell recommending what it should do.</p>
<p>While researchers have shown that <a href="https://doi.org/10.3390/ijms19123851">signals from AHR</a> influence multiple sclerosis development, how it does so is unclear. To better understand what AHR is doing specifically in the guts of patients with MS, we genetically engineered mice that are missing AHR in some of their immune cells. By silencing AHR’s activity, we could understand what role it may be playing in autoimmunity.</p>
<p>We expected to learn more from this experiment about the molecular communication of immune cells. Instead we found something surprising: The gut environment in these mice <a href="https://doi.org/10.1371/journal.pbio.3002000">had changed</a>. Specifically, the chemical composition of their guts had been altered, indicating that the metabolism of gut bacteria had shifted. This meant that AHR is not only sensing what’s going on in the gut, but the receptor is also actively shaping its environment.</p>
<figure>
<iframe width="440" height="260" src="https://www.youtube.com/embed/gnZEge78_78?wmode=transparent&start=0" frameborder="0" allowfullscreen=""></iframe>
<figcaption><span class="caption">The gut contains the largest number of immune cells in the body.</span></figcaption>
</figure>
<p>More importantly, we found that mice without AHR were able to recover from MS. In our mouse model of MS, we induced autoimmunity by immunizing mice against myelin, the protective layer surrounding neurons. This meant that the immune system of the mice was primed to attack myelin, leading to the poor muscle control and paralysis seen in MS. We wanted to test whether the gut microbiome played a role in why mice without AHR were able to recover. When we transplanted the gut bacteria from the digestive tracts of mice without AHR into mice with AHR, we found that the mice with AHR were also able to recover from paralysis. This meant that the gut microbiome was driving recovery from MS.</p>
<p>We also found that the guts of mice without AHR had high levels of <a href="https://www.healthline.com/health/bile-salts">bile acids</a> – chemicals produced in the liver and secreted into the intestines that help with digestion. Bile acids are often broken down by the resident bacteria in the gut. </p>
<p>One bile acid in particular, called taurocholic acid, was especially concentrated in mice without AHR. To test whether taurocholic acid offered protection against MS, we fed this chemical to mice with AHR as they started to develop autoimmunity to myelin. While control mice that were fed saline became paralyzed from the waist down, the mice that were fed taurocholic acid just got a little wobbly before they recovered.</p>
<p>With further investigation, we discovered that these mice were able to recover their motor control because their immune cells were not as strong. Exposing their immune cells to bile acids shortened the life span of the cells, thus preventing them from causing as much damage to myelin and motor neurons.</p>
<p>While we still do not understand why bile acids weaken immune cells, we believe it may be a key step to understanding how to interrupt autoimmunity in MS and other autoimmune disorders.</p>
<h2>Better treatments for multiple sclerosis</h2>
<p>Current available therapies for autoimmune disorders like MS are <a href="https://www.nationalmssociety.org/Treating-MS/Medications">immunosuppressant drugs</a> that quiet the immune response. While these drugs can reduce relapse and delay disease progression, they can also put patients at high risk of infection and difficult side effects. With the <a href="https://www.nationalmssociety.org/coronavirus-covid-19-information">COVID-19 pandemic</a>, the danger of having a weakened immune system has become even more apparent. </p>
<p>Finding other avenues to quiet an overactive immune system, such as through bile acids, could help researchers create safer drugs that could help prevent or treat disease. The body produces eight different bile acids that each have different chemical properties. Our team is working to identify whether taurocholic acid is truly the best option for treating MS or if another bile acid – or a combination of several – would be more effective. </p>
<p>Bile acids are far from ready to be used as treatment in people. But we believe that the key to preventing multiple sclerosis may be inside us already.</p><img src="https://counter.theconversation.com/content/200199/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Andrea Merchak receives funding from National Institutes of Health grant R33 MH108156, National Institutes of Health grant T32 NS115657, The Owens Family Foundation, UVA Trans University Microbiome Initiative pilot grant.
</span></em></p>The gut microbiome plays a big role in mediating how the immune system responds to perceived threats, which include the body’s own nerves.Andrea Merchak, Ph.D. Candidate in Neuroscience, University of VirginiaLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1998852023-02-21T04:10:31Z2023-02-21T04:10:31ZCrusty, blistering and peeling: where do cold sores come from and what can you do about them?<figure><img src="https://images.theconversation.com/files/510774/original/file-20230217-20-hr3tx5.jpg?ixlib=rb-1.1.0&rect=7%2C0%2C4913%2C3253&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">
</span> <span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/part-young-womans-face-virus-herpes-1165988803">www.shutterstock.com</a></span></figcaption></figure><p>Three quarters of <a href="http://conditions.health.qld.gov.au/HealthCondition/condition/14/188/62/genital-herpes">Australians</a> are living with herpes simplex virus type 1 (<a href="https://www.who.int/news-room/fact-sheets/detail/herpes-simplex-virus">HSV-1</a>), an infection which causes cold sores. These tiny fluid-filled <a href="https://www.mayoclinic.org/diseases-conditions/cold-sore/symptoms-causes/syc-20371017">lesions</a> and blisters sit along the mouth and nose area. </p>
<p>This is not the same virus that causes genital herpes, <a href="https://www.who.int/news-room/fact-sheets/detail/herpes-simplex-virus">HSV-2</a>, which is present in about 13% of people worldwide. </p>
<p>In most cases, the body is quite good at suppressing HSV-1 with help from the immune system. This means that not everyone with the virus knows they have it.</p>
<p>However, sometimes the virus can overwhelm the system and present as a cold sore, which is a highly contagious sore on the mouth.</p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/what-causes-dry-lips-and-how-can-you-treat-them-does-lip-balm-actually-help-161264">What causes dry lips, and how can you treat them? Does lip balm actually help?</a>
</strong>
</em>
</p>
<hr>
<h2>Always at the worst time</h2>
<p>Around 92% of us have viruses inside our systems from past <a href="https://bmcbiol.biomedcentral.com/articles/10.1186/s12915-014-0071-7">infections</a>. For most people, these are <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3142679/">latent viruses</a>, which do not cause any concerns until reactivated.</p>
<p>While we can keep these viruses from <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3142679/">reactivating</a> and causing any issues, most of the time, exhaustion, physical exertion, as well as psychological stress, can <a href="https://www.sciencedirect.com/science/article/pii/S0306987700912192">suppress</a> elements of the immune system. This leaves our body weakened, and opens the door for viruses.</p>
<p>Common reactivation of latent viruses include those that cause <a href="https://www.betterhealth.vic.gov.au/health/conditionsandtreatments/glandular-fever">glandular fever</a>, as well as <a href="https://pubmed.ncbi.nlm.nih.gov/31090135/">chicken pox</a>/<a href="https://www.mayoclinic.org/diseases-conditions/shingles/symptoms-causes/syc-20353054">shingles</a>.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/510780/original/file-20230217-24-gjujtb.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="Man coughing, holding his hand up" src="https://images.theconversation.com/files/510780/original/file-20230217-24-gjujtb.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/510780/original/file-20230217-24-gjujtb.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/510780/original/file-20230217-24-gjujtb.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/510780/original/file-20230217-24-gjujtb.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/510780/original/file-20230217-24-gjujtb.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/510780/original/file-20230217-24-gjujtb.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/510780/original/file-20230217-24-gjujtb.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=503&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Dormant viruses can cause many more problems when they become active.</span>
<span class="attribution"><a class="source" href="https://unsplash.com/photos/C-zwLtPSErc">Unsplash</a>, <a class="license" href="http://creativecommons.org/licenses/by/4.0/">CC BY</a></span>
</figcaption>
</figure>
<p>When HSV-1 reactivates, it may present as cold sores.</p>
<p>This usually starts as a tingling, itching, or burning sensation around the mouth, lips, or nose. Fluid-filled blisters will subsequently form, which dry out and leave a crust after about a week. The scab then flakes off and will typically heal within one to <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8706154/">two weeks</a> without leaving a scar.</p>
<p>Along with cold sores, other common symptoms of an active HSV-1 infection can include fever, nausea, headaches, sore throat, or swollen glands.</p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/curious-kids-how-do-scabs-form-151586">Curious Kids: how do scabs form?</a>
</strong>
</em>
</p>
<hr>
<h2>Cold sores can get anyone</h2>
<p>Viruses can be spread quickly and easily. As such, if we do have an infection, preventing its spread is important.</p>
<p>Babies and children are particularly vulnerable. Around <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4489118/">38%</a> of mothers kiss their babies on the lips, and 14% share a spoon with them. These practices can spread HSV-1, particulary in the first four weeks <a href="https://www.nhs.uk/conditions/neonatal-herpes/">after birth</a>, when a baby has the weakest immune defences. </p>
<p>As a general rule, to prevent spreading any infections, always avoid kissing a baby on the lips.</p>
<figure class="align-center ">
<img alt="Baby" src="https://images.theconversation.com/files/510459/original/file-20230216-22-25drnf.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/510459/original/file-20230216-22-25drnf.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=434&fit=crop&dpr=1 600w, https://images.theconversation.com/files/510459/original/file-20230216-22-25drnf.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=434&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/510459/original/file-20230216-22-25drnf.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=434&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/510459/original/file-20230216-22-25drnf.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=545&fit=crop&dpr=1 754w, https://images.theconversation.com/files/510459/original/file-20230216-22-25drnf.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=545&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/510459/original/file-20230216-22-25drnf.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=545&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">Babies still have developing immune systems.</span>
<span class="attribution"><span class="source">Christian Moro, Author provided</span></span>
</figcaption>
</figure>
<p>Sun <a href="https://www.sciencedirect.com/science/article/pii/B9781437717938000182">exposure</a> and cool weather encourage cold sores to appear, as the conditions can dry out the lips and damage the skin, creating a favourable environment for the virus.</p>
<p>Some treatments are available. If you are having trouble with cold sores, you can ask a doctor or pharmacist to outline some options for <a href="https://linkinghub.elsevier.com/retrieve/pii/0166-3542(93)90094-Y">antiviral</a> medicines. These impact the virus’ ability to reactivate, replicate, and divide.</p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/why-are-my-hands-and-feet-always-cold-and-when-should-i-be-worried-184154">Why are my hands and feet always cold? And when should I be worried?</a>
</strong>
</em>
</p>
<hr>
<h2>So I have a cold sore, what should I do?</h2>
<p>Unfortunately, there is no cure for the underlying virus. But if you do have a cold sore, here are some things you can do to help:</p>
<ul>
<li>keep your hands clean and don’t touch the sores</li>
<li>avoid <a href="https://theconversation.com/can-eating-hot-chilli-peppers-actually-hurt-you-163489">spicy</a> or acidic foods to minimise burning sensations</li>
<li>seek over-the-counter or prescription <a href="https://linkinghub.elsevier.com/retrieve/pii/0166-3542(93)90094-Y">antiviral</a> tablets or creams</li>
<li>remain hydrated</li>
<li>wear sunscreen and avoid direct sun exposure</li>
<li>cover-up during <a href="https://theconversation.com/why-do-i-need-to-pee-more-in-the-cold-184236">cold</a> or dry weather</li>
<li>avoid kissing or sharing anything with your saliva to minimise spreading.</li>
</ul>
<p>If you are concerned about your cold sores (for example, if the gums become swollen, the wound weeps pus, or you get a <a href="https://www.youtube.com/watch?v=BxgEoLmOACo">fever</a>), seek advice from your family doctor.</p>
<p>While many people carry HSV-1, not everyone will get cold sores. For those who do, looking after yourself is key. <a href="https://synapse.koreamed.org/articles/1095278">Eating</a> healthy, <a href="https://theconversation.com/what-position-should-i-sleep-in-and-is-there-a-right-way-to-sleep-189873">sleeping well</a>, and noticing when our bodies are telling us to take a step back and relax goes a long way towards keeping latent viruses at bay.</p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/what-position-should-i-sleep-in-and-is-there-a-right-way-to-sleep-189873">What position should I sleep in, and is there a ‘right’ way to sleep?</a>
</strong>
</em>
</p>
<hr>
<img src="https://counter.theconversation.com/content/199885/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>The authors do not work for, consult, own shares in or receive funding from any company or organisation that would benefit from this article, and have disclosed no relevant affiliations beyond their academic appointment.</span></em></p>Three quarters of Australians are living with HSV-1, with cold sores tending to appear at the most inconvenient times.Christian Moro, Associate Professor of Science & Medicine, Bond UniversityCharlotte Phelps, PhD Candidate, Health Science and Medicine, Bond UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1985372023-02-08T14:28:15Z2023-02-08T14:28:15ZHow do I improve my immunity? Expert shares tips on what to do - and what to avoid<figure><img src="https://images.theconversation.com/files/507107/original/file-20230130-7241-9z07f6.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Exercising regularly, and spending time outdoors can improve your health. </span> <span class="attribution"><span class="source">Shutterstock</span></span></figcaption></figure><p>The human immune system is arguably the most complex system in the human body. But scientists have made a lot of progress in understanding how it functions.</p>
<p>That’s important for understanding illnesses and how to manage them. For instance, it’s important to understand that an immune response takes several days to fully develop. This knowledge would hopefully prevent people from getting impatient and seeking inappropriate care. </p>
<p>The immune system is made up of an intricate network of cells, tissues and molecules. These control the delicate balance between eliminating cancerous or infected cells, and not harming the body in the process. </p>
<p>A poorly functioning immune system can cause a variety of health problems. </p>
<p>It could lead to a person getting recurrent infections. Depending on the nature of the immune deficiency, the infections can range from viral (such as colds, flu, shingles and fever blisters) to bacterial (such as tuberculosis) or fungal (such as thrush). </p>
<p>Immune system dysfunction can also present as excessive inflammation or even auto-immunity. In this case the body starts seeing its own tissues as foreign and attacks them. Some examples of these conditions are rheumatoid arthritis, lupus and psoriasis.</p>
<p>The factors that affect our immune system range from things we can’t change, such as our genetic make-up and exposure to past pathogens, to things we may be able to control or modify.</p>
<p>I am an immunologist, and in this article I unpack the changes you can make today to help your immune system function better. They include diet, managing stress levels, and limiting exposure to environmental factors, such as germs, pollution and toxins. </p>
<p>Optimal immune function plays an important role in maintaining health. Given the immense complexity of the immune system, simplistic solutions are not effective. It’s important to understand some of the things you should – and shouldn’t – do. </p>
<h2>What not to do</h2>
<p>Many products claim to “boost” the immune system. But given the complex interplay between the cells in our bodies, it’s not really possible to “boost” just one part of the immune system. </p>
<p>And even if it was possible, “boosting” one aspect of your immune system can set off bad reactions by upsetting the delicate balance that makes up our bodies. For instance, “boosting” the immune system’s ability to fight infection could also “boost” other aspects, such as inflammation, that could harm normal tissue. </p>
<p>It is true that the immune system relies on vitamins and minerals to perform its tasks. But there is no solid evidence that taking vitamins and mineral supplements will improve its functioning. </p>
<p>The exception is when a person has a known deficiency, such as vitamin D deficiency. Most people with vitamin D deficiency do not have any symptoms or only have vague, non-specific symptoms, such as tiredness or lower back ache. People living with osteoporosis, diabetes, kidney disease, obesity, or depression, or those with limited sun exposure, especially the elderly, are at increased risk of having a deficiency. It’s important to address the problem because it can increase the risk of fractures, as well as infection from various pathogens, especially those affecting the lungs, such as flu and SARS-CoV-2. </p>
<p>If you think you’ve got a nutrient deficiency you should consult a healthcare practitioner for an accurate diagnosis. They can set out an evidence-based management strategy for you. </p>
<p>The reason for seeking professional help is that dosing up on supplements can be bad for you. </p>
<p>Firstly, some vitamins, such as vitamin A, D, E and K, are fat-soluble and are stored in the body. It is therefore possible to have levels that are too high, which can cause its own problems. For instance, too-high levels of vitamin D can cause kidney stones, constipation and high blood pressure. Too much vitamin A or iron can cause damage to the liver and other organs. </p>
<p>Secondly, nutrients should not be seen as independent components. Rather they should be seen as parts of a whole. Many supplements can interact negatively with other supplements and even with medication. For instance, vitamin K can reduce the ability of the blood thinner warfarin to prevent blood clots.</p>
<p>Combining different supplements can also lead to excessive or inadequate amounts of certain nutrients, with potentially detrimental effects. For example, prolonged zinc supplementation can cause copper deficiency, which has been linked to anaemia and impaired brain function. </p>
<h2>What to do</h2>
<p>The best way to ensure that your immune system gets what it needs is through a healthy and balanced lifestyle. </p>
<p>Diet is critical. Eat food that is unprocessed, preservative-free, and rich in a variety of vitamins, minerals and antioxidants. Your diet should include green and yellow vegetables, fruit and berries, whole grains, seeds and nuts. </p>
<p>And it’s not just the individual components of food that are important. The interplay between them matters too. This is something that cannot be reproduced in a tablet. </p>
<p>Lifestyle factors are also key. Stress is a normal and essential part of life, but it must be switched off to protect the body. Finding effective ways to control stress, such as breathing exercises, yoga and meditation, is important. </p>
<p>Activities that have been shown to improve health include getting enough rest, exercising regularly, spending time outdoors, and staying connected socially. Smoking and excessive alcohol use are clearly harmful. </p>
<p>Finally, we often forget to be kind to ourselves. When you are ill, take time to recover. When you are going through an especially stressful time, make an extra effort to de-stress. </p>
<p>Most importantly, don’t regard these as emergency measures. Make them part of your lifestyle. As tempting as it may be, it is not possible to “supplement” yourself out of a bad lifestyle.</p><img src="https://counter.theconversation.com/content/198537/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Theresa Rossouw does not work for, consult, own shares in or receive funding from any company or organisation that would benefit from this article, and has disclosed no relevant affiliations beyond their academic appointment.</span></em></p>As tempting as it is, it is not possible to “supplement” oneself out of a bad lifestyle.Theresa Rossouw, Professor, University of PretoriaLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1971512023-01-09T11:12:07Z2023-01-09T11:12:07ZColds, flu and COVID: how diet and lifestyle can boost your immune system<figure><img src="https://images.theconversation.com/files/503417/original/file-20230106-9921-bqlyvc.jpg?ixlib=rb-1.1.0&rect=44%2C11%2C7425%2C4973&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Most of us are eager to avoid getting sick this time of year.</span> <span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/young-sick-woman-sitting-on-sofa-667211476">baranq/ Shutterstock</a></span></figcaption></figure><p>Every day we are exposed to a wide array of potentially harmful microorganisms – such as colds, the flu and even COVID. But our <a href="https://www.niaid.nih.gov/research/immune-system-overview">immune system</a> – a network of intricate pathways within our body – helps protect us against these microorganisms and other potential diseases. Essentially, it recognises foreign invaders, such as viruses and bacteria, and takes immediate action to defend us.</p>
<p>Humans have two types of immunity: innate and adaptive. <a href="https://www.niaid.nih.gov/research/immune-system-overview">Innate immunity</a> is the body’s first-line of defence, primarily consisting of physical barriers (such as skin), and secretions – including mucus, stomach acid and enzymes in saliva and sweat which prevent microorganisms getting inside the body. It also consists of cells that attack all foreign invaders entering the body.</p>
<p><a href="https://www.niaid.nih.gov/research/immune-system-overview">Adaptive immunity</a> is a system that learns to recognise a pathogen. It’s regulated by cells and organs in our body such as the spleen, thymus, bone marrow and lymph nodes. When a foreign substance enters the body, these cells and organs create antibodies and <em>multiply</em> the immune cells specific to that harmful substance in order to attack and destroy it. They also remember the pathogen for future reference.</p>
<p>There are many things we can do to support our immune system and even improve its function. Simple changes to your diet and lifestyle can all play a big role in helping you avoid getting sick.</p>
<h2>We are what we eat</h2>
<p>The nutrients we get from the foods in our diet play key roles in both building and maintaining our immune system.</p>
<p>Take for example the amino acid <a href="https://academic.oup.com/jn/article/137/6/1681S/4664953?login=false">arginine</a>. This is essential for generating nitric oxide within immune cells, which is an important defence molecule against organisms. <a href="https://pubmed.ncbi.nlm.nih.gov/33377367/">Vitamin A and zinc</a> are crucial in the rapid reproduction of immune cells. <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5707683/">Vitamin C</a> contributes to immune defence by supporting the cell functions of both immune systems. Similarly, <a href="https://www.mdpi.com/2072-6643/10/11/1614">vitamin E</a> has been shown to enhance immune responses in animals and humans and to provide protection against several infectious diseases, such as flu, COVID and the common cold. </p>
<p>A varied diet including fruits and vegetables, wholegrains, nuts, seeds, dairy products, as well as fish, meat, or plant protein alternatives, will all contain these key nutrients which support our immune health.</p>
<p>The vast combination of microorganisms that live in our gut – <a href="https://ep.bmj.com/content/102/5/257">known as our microbiome</a> – also have significant effects on our health and wellbeing, despite their tiny size. In fact, the microbiome is often referred to as the “<a href="https://www.sciencefocus.com/the-human-body/a-gut-feeling-meet-your-second-brain/">second brain</a>” due to the extensive relationship it has with the body’s organs and systems. </p>
<p>One particular role the microbes in our gut play is supporting <a href="https://www.nature.com/articles/s41422-020-0332-7">immune function</a>. They help to control inflammation, the process the immune system uses to protect us from harmful pathogens. Ensuring the microbiome is healthy can improve immune function.</p>
<figure class="align-center ">
<img alt="A bowl of greens with a two pieces of grilled salmon on top." src="https://images.theconversation.com/files/503419/original/file-20230106-21-oixeb2.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/503419/original/file-20230106-21-oixeb2.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/503419/original/file-20230106-21-oixeb2.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/503419/original/file-20230106-21-oixeb2.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/503419/original/file-20230106-21-oixeb2.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/503419/original/file-20230106-21-oixeb2.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/503419/original/file-20230106-21-oixeb2.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=503&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">The Mediterranean diet can help support the microbiome.</span>
<span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/grilled-salmon-fillet-fresh-vegetable-salad-1934626109">Sea Wave/ Shutterstock</a></span>
</figcaption>
</figure>
<p>There are many ways we can support our microbiome through the foods we eat. For example, research has shown <a href="https://www.mdpi.com/1422-0067/19/12/3720">a Mediterranean diet</a>, which is rich in vitamins, minerals and dietary fibre, has an anti-inflammatory effect in the gut, which can help boost the body’s immune function. </p>
<p>This effect may be explained by a strain of bacteria known as <em>Faecalibacterium prausnitzii</em> which is <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7359750/">key to immune regulation</a>. This bacteria tends to be low in the western diet but abundant in the Mediterranean diet. You should also avoid too many refined cereals, sugars and animal fats, which can all <a href="https://www.nature.com/articles/nm.3444">heighten inflammation</a> in the body which weakens the immune response.</p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/mediterranean-diet-increases-gut-bacteria-linked-to-healthy-ageing-in-older-adults-131928">Mediterranean diet increases gut bacteria linked to healthy ageing in older adults</a>
</strong>
</em>
</p>
<hr>
<p>Probiotics (supplementary blends of live bacteria) may also have benefits. Research has even shown a probiotic blend of bacterial strains <em>Lactiplantibacillus plantarumand</em> and <em>Pediococcus acidilactici</em> <a href="https://www.tandfonline.com/doi/full/10.1080/19490976.2021.2018899">reduced the amount of virus</a> detected in the nose and lungs, as well as the duration of symptoms, in COVID patients.</p>
<h2>Living a healthy lifestyle</h2>
<p>Your lifestyle can also have a big affect on immune function.</p>
<p>For example, smoking <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5352117/">affects both innate and adaptive immunity</a>, causing it to both overreact to pathogens and lower it’s immunity defences. Alcohol has also been shown to increase susceptibility to <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4590612/">both bacterial and viral infections</a>. It does this by altering the way our immune system defends against infections. Even moderate drinkers may have lower immunity. </p>
<p>Sleep is also crucial for maintaining immune function. Studies show that frequent, poor sleep causes inflammation in the body. This may worsen immune response, <a href="https://www.nature.com/articles/s42003-021-02825-4">increasing infection risk</a> and worsening infections. Adolescents who only get around six hours of sleep are also more likely to suffer from common illnesses, such as <a href="https://onlinelibrary.wiley.com/doi/10.1111/jsr.12096">cold, flu and gastroenteritis</a>.</p>
<p>Stress is another factor known to have a large impact on the immune system. It isn’t just chronic stress that suppresses the immune system either – even <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1361287/">brief periods of stress</a> (such as an exam) can worsen immune function. Fortunately, mindfulness meditation (which can help manage stress) may be <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4940234/">beneficial for the immune system</a> – though it isn’t entirely clear yet why.</p>
<p>Exercise has also been shown to affect immune function, with research showing <a href="https://journals.physiology.org/doi/full/10.1152/physrev.2000.80.3.1055?rfr_dat=cr_pub++0pubmed&url_ver=Z39.88-2003&rfr_id=ori%3Arid%3Acrossref.org">moderate-intensity physical activity</a> in particular (such as a brisk walk or ballroom dancing) can improve immune response. However, it’s important to strike the right balance as long, intense exercise without sufficient rest between workouts can actually worsen immune function and make you more likely to catch an infection. And according to some data, this decrease can happen after only <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7387807">90 minutes</a> of moderate- to high-intensity physical activity. </p>
<p>Of course, <a href="https://www.who.int/news-room/questions-and-answers/item/vaccines-and-immunization-what-is-vaccination">vaccination</a> remains the best way to prevent infection from many common diseases, such as the flu. But a good diet and lifestyle – alongside other <a href="https://www.gov.uk/government/publications/health-protection-in-schools-and-other-childcare-facilities/preventing-and-controlling-infections">preventative measures</a>, such as washing your hands or wearing a face mask – help support your immune system and the effectiveness of vaccines.</p><img src="https://counter.theconversation.com/content/197151/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Philippe B. Wilson is Chief Scientific Officer of NHS Willows Health.</span></em></p><p class="fine-print"><em><span>Samuel J. White does not work for, consult, own shares in or receive funding from any company or organisation that would benefit from this article, and has disclosed no relevant affiliations beyond their academic appointment.</span></em></p>Here are some simple things you can do everyday to help your immune system fight off infections.Samuel J. White, Senior Lecturer in Genetic Immunology, Nottingham Trent UniversityPhilippe B. Wilson, Professor of One Health, Nottingham Trent UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1957182022-12-16T13:13:54Z2022-12-16T13:13:54Z1918 flu pandemic upended long-standing social inequalities – at least for a time, new study finds<figure><img src="https://images.theconversation.com/files/499388/original/file-20221206-16-lo9q7q.jpg?ixlib=rb-1.1.0&rect=0%2C220%2C3000%2C1742&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">In this November 1918 photo, a nurse tends to a patient in the influenza ward of the Walter Reed hospital in Bethesda, Md. </span> <span class="attribution"><a class="source" href="https://newsroom.ap.org/detail/VirusOutbreak1918InfluenzaCOVID19/97d84472fcad44449444ae3b7cc5f539/photo?Query=1918%20flu&mediaType=photo&sortBy=&dateRange=Anytime&totalCount=91&currentItemNo=29">AP Photo/Harris & Ewing via Library of Congress</a></span></figcaption></figure><p><em>The <a href="https://theconversation.com/us/topics/research-brief-83231">Research Brief</a> is a short take about interesting academic work.</em> </p>
<h2>The big idea</h2>
<p>Racial disparities in <a href="https://doi.org/10.1215/00703370-10235825">influenza deaths shrunk by 74% in U.S. cities</a> during the <a href="https://www.cdc.gov/flu/pandemic-resources/1918-pandemic-h1n1.html">1918 flu pandemic</a> due to an odd coincidence of virus and history. That’s the key finding of our recently published study in the journal Demography. </p>
<p>This conclusion contradicts the <a href="https://tidsskriftet.no/2017/05/global-helse/social-inequality-forgotten-factor-pandemic-influenza-preparedness">common claim</a> that crises like pandemics <a href="https://doi.org/10.1073/pnas.2020685118">make social inequalities worse</a>. The 1918 influenza pandemic was a surprising exception. </p>
<p>Prior to the 1918 pandemic, Black people in the U.S. died of respiratory diseases <a href="https://doi.org/10.1007/s13524-019-00789-z">at vastly higher rates</a> than white people. But our study found that urban white people in their 20s and 30s were especially vulnerable to the 1918 virus, dying at rates that were up to 20 times higher than normal. While the death rates of Black people in urban settings also spiked during the 1918 pandemic, they did so by a much smaller rate than in white populations. On average, across all age groups, white mortality increased fivefold, while Black mortality increased threefold.</p>
<p>Overall, Black people <a href="https://doi.org/10.7326/M20-2223">still died at higher rates</a> than white people during the 1918 pandemic, but the ratio of Black-to-white mortality – a measure of racial inequality – <a href="https://doi.org/10.3390/ijerph16142487">shrank dramatically</a> compared with other time periods. So while 1918 was wildly deadly across the world, the death rate among urban white young adults in the U.S. was truly unprecedented.</p>
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<h2>Why it matters</h2>
<p>One anomalous feature of the pandemic is well known: It <a href="https://doi.org/10.1371/journal.pone.0069586">killed many young adults</a> alongside children and elderly people, who are traditionally at risk from flu viruses.</p>
<p>But the unusually small racial inequality in flu deaths in the U.S. in 1918 is a little-known puzzle that contrasts with modern pandemics <a href="https://doi.org/10.1073/pnas.2205813119">like COVID-19</a> <a href="https://doi.org/10.2105/AJPH.2009.170241">and HIV</a>, which have hit Black communities especially hard. It also contrasts with a global tendency for <a href="https://doi.org/10.1186/s13643-018-0931-2">poorer populations to be more likely</a> to die from the flu.</p>
<p>Our study considered several hypotheses to explain the surprising patterns in the U.S. during the 1918 pandemic. One such potential explanation was that policies like school closures especially benefited Black populations because of their higher risk of dying from the flu in nonpandemic years when such measures were absent.</p>
<p>But only one explanation fits our evidence: Urban white young adults in the U.S. were deeply vulnerable in 1918 because of the way their immune systems had been programmed during childhood in the late 19th century. This is because the first flu people encounter as children is special: <a href="https://doi.org/10.1126/science.aag1322">It teaches the immune system</a> how to respond to future flu infections. However, research shows that this so-called immunological imprinting <a href="https://doi.org/10.1016/j.jaut.2017.04.008">can be harmful</a> when the virus someone later encounters is very different from the virus their immune system has been trained against.</p>
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<figcaption><span class="caption">The 1918 flu pandemic killed at least 50 million people worldwide.</span></figcaption>
</figure>
<p>The last flu pandemic to hit U.S. cities before 1918 was a <a href="https://doi.org/10.1073/pnas.1000886107">devastating global pandemic</a> that began in 1889. Exposure to that virus would have taught children’s immune systems to expect <a href="https://doi.org/10.1073/pnas.1324197111">what was probably an H3N8 flu</a>. But the devastation in 1918 was caused by the world’s first H1N1 pandemic. The two strains belong to two different groups of influenza viruses, and immune protection from H3N8 would not have conferred protection against H1N1. </p>
<p>To the contrary: People whose first flu exposure occurred in the 1890s would have likely had a compromised immune response to the 1918 pandemic because their immune system produced the wrong kind of antibodies that <a href="https://doi.org/10.1038/s41467-021-23977-1">crowded out more effective ones</a>.</p>
<p>In <a href="https://doi.org/10.1371/journal.pone.0069586">2013</a> and <a href="https://doi.org/10.1073/pnas.1324197111">2014</a> studies, two groups of virologists and demographers proposed and tested the hypothesis that 1890s imprinting explains the unusually high mortality of young adults during the 1918 pandemic. We adapted their argument to explain unusually small racial disparities as well. </p>
<p>This hypothesis suggests that the pattern of Black and white deaths in 1918 revolves around a historical coincidence. Black young adults were more often spared this fateful imprinting because they spent their childhoods in rural areas. As a result, though they often lived in deep poverty, they did not encounter some of the respiratory diseases that were rampant in cities. So while they were vulnerable to 1918’s novel flu, they were less so than people whose immune systems were primed to meet a virus like the one that circulated in the 1890s. </p>
<h2>What still isn’t known</h2>
<p>Immunologists are only beginning to understand the exact mechanisms through which imprinting affects long-term immune responses. Recent studies about the <a href="https://doi.org/10.3390/v11020122">early 20th century</a> and the <a href="https://doi.org/10.1038/s41467-021-23977-1">COVID-19 pandemic</a> support the idea that imprinting can significantly affect immune responses later in life. We all carry in our bodies the memories of our past disease exposures. </p>
<p>Those exposures <a href="https://doi.org/10.1007/s13524-019-00789-z">changed radically</a> during the 20th century, and the full consequences for population immunity in the COVID-19 era remain to be unraveled.</p><img src="https://counter.theconversation.com/content/195718/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Elizabeth Wrigley-Field receives funding from the Minnesota Population Center, which is funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development (grant number P2C HD041023).</span></em></p><p class="fine-print"><em><span>Martin Eiermann does not work for, consult, own shares in or receive funding from any company or organization that would benefit from this article, and has disclosed no relevant affiliations beyond their academic appointment.</span></em></p>During the 1918 flu pandemic, white people died at similar rates to Black Americans, according to a new study – a very different pattern than what occurred during the COVID-19 pandemic.Elizabeth Wrigley-Field, Assistant Professor of Sociology, University of MinnesotaMartin Eiermann, Postdoctoral Fellow in Sociology, Duke UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1925672022-12-14T13:14:47Z2022-12-14T13:14:47ZNasal vaccines promise to stop the COVID-19 virus before it gets to the lungs – an immunologist explains how they work<figure><img src="https://images.theconversation.com/files/493959/original/file-20221107-19718-xu583n.jpg?ixlib=rb-1.1.0&rect=0%2C11%2C7360%2C4891&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Nasal vaccines for COVID-19 are still in early development.</span> <span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/photo/little-cute-blonde-boy-getting-vaccinated-covid-19-royalty-free-image/1282728128?phrase=COVID-19%20nasal%20vaccine&adppopup=true">Paul Biris/Moment via Getty Images</a></span></figcaption></figure><p><em>The Pfizer-BioNTech and Moderna mRNA vaccines have played a large role in preventing deaths and severe infections from COVID-19. But researchers are still in the process of developing alternative approaches to vaccines to improve their effectiveness, including how they’re administered. Immunologist and microbiologist <a href="https://www.researchgate.net/profile/Michael-Russell-10">Michael W. Russell</a> of the University at Buffalo explains how nasal vaccines work, and where they are in the development pipeline.</em></p>
<h2>How does the immune system fight pathogens?</h2>
<p>The immune system has two distinct components: mucosal and circulatory.</p>
<p>The <a href="http://dx.doi.org/10.1016/B978-0-12-415847-4.00001-X">mucosal immune system</a> provides protection at the mucosal surfaces of the body. These include the mouth, eyes, middle ear, the mammary and other glands, and the gastrointestinal, respiratory and urogenital tracts. Antibodies and a variety of other anti-microbial proteins in the <a href="https://theconversation.com/slime-is-all-around-and-inside-you-new-research-on-its-origins-offers-insight-into-genetic-evolution-189278">sticky secretions</a> that cover these surfaces, as well as immune cells located in the lining of these surfaces, directly attack invading pathogens.</p>
<p>The <a href="https://doi.org/10.1186/1741-7007-8-84">circulatory part of the immune system</a> generates antibodies and immune cells that are delivered through the bloodstream to the internal tissues and organs. These circulating antibodies do not usually reach the mucosal surfaces in large enough amounts to be effective. Thus mucosal and circulatory compartments of the immune system are largely <a href="http://dx.doi.org/10.3389/fimmu.2022.957107">separate and independent</a>.</p>
<h2>What are the key players in mucosal immunity?</h2>
<p>The immune components people may be most familiar with are proteins known as <a href="https://www.ncbi.nlm.nih.gov/books/NBK513460/">antibodies, or immunoglobulins</a>. The immune system generates antibodies in response to invading agents that the body identifies as “non-self,” such as viruses and bacteria.</p>
<p>Antibodies bind to specific antigens: the part or product of a pathogen that induces an immune response. Binding to antigens allows antibodies to either inactivate them, as they do with toxins and viruses, or kill bacteria with the help of additional immune proteins or cells.</p>
<p>The mucosal immune system generates a specialized form of antibody called <a href="http://dx.doi.org/10.1038/mi.2011.39">secretory IgA, or SIgA</a>. Because SIgA is located in mucosal secretions, such as saliva, tears, nasal and intestinal secretions, and breast milk, it is resistant to digestive enzymes that readily destroy other forms of antibodies. It is also superior to most other immunoglobulins at neutralizing viruses and toxins, and at preventing bacteria from attaching to and invading the cells lining the surfaces of organs.</p>
<p>There are also many <a href="http://dx.doi.org/10.1002/9780470015902.a0000942.pub2">other key players</a> in the mucosal immune system, including different types of anti-microbial proteins that kill pathogens, as well as immune cells that generate antibody responses.</p>
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<figcaption><span class="caption">Mucus is one of the central secretions of the mucosal immune system.</span></figcaption>
</figure>
<h2>How does the COVID-19 virus enter the body?</h2>
<p>Almost all infectious diseases in people and other animals are <a href="https://www.ncbi.nlm.nih.gov/books/NBK209710/">acquired through mucosal surfaces</a>, such as by eating or drinking, breathing or sexual contact. Major exceptions include infections from wounds, or pathogens delivered by insect or tick bites.</p>
<p>The virus that causes COVID-19, SARS-CoV-2, enters the body via droplets or aerosols that get into your <a href="http://dx.doi.org/10.1038/s41385-020-00359-2">nose, mouth or eyes</a>. It can cause severe disease if it descends deep into the lungs and causes an <a href="https://theconversation.com/long-covid-19-and-other-chronic-respiratory-conditions-after-viral-infections-may-stem-from-an-overactive-immune-response-in-the-lungs-186970">overactive, inflammatory immune response</a>.</p>
<p>This means that the virus’s first contact with the immune system is probably through the surfaces of the nose, mouth and throat. This is supported by the presence of SIgA antibodies against SARS-CoV-2 <a href="http://dx.doi.org/10.3389/fimmu.2020.611337">in the secretions of infected people</a>, including their saliva, nasal fluid and tears. These locations, especially the tonsils, have specialized areas that specifically trigger mucosal immune responses.</p>
<p><a href="http://dx.doi.org/10.3390/pathogens11040397">Some research suggests</a> that if these SIgA antibody responses form as a result of vaccination or prior infection, or occur quickly enough in response to a new infection, they could prevent serious disease by confining the virus to the upper respiratory tract until it is eliminated.</p>
<h2>How do nasal vaccines work?</h2>
<p>Vaccines can be <a href="http://dx.doi.org/10.1016/B978-0-12-415847-4.00055-0">given through mucosal routes</a> via the mouth or nose. This induces an immune response through areas that stimulate the mucosal immune system, leading mucosal secretions to produce SIgA antibodies.</p>
<p>There are <a href="http://dx.doi.org/10.1016/B978-0-12-811924-2.00001-8">several existing mucosal vaccines</a>, most of them taken by mouth. Currently only one, the flu vaccine, is delivered nasally.</p>
<p>In the case of nasal vaccines, the viral antigens intended to stimulate the immune system would be taken up by immune cells within the lining of the nose or tonsils. While the exact mechanisms by which nasal vaccines work in people have not been thoroughly studied, researchers believe they <a href="http://dx.doi.org/10.1007/BF00915547">work analogously to oral mucosal vaccines</a>. Antigens in the vaccine induce B cells in mucosal sites to mature into plasma cells that secrete a form of IgA. That IgA is then transported into mucosal secretions throughout the body, where it becomes SIgA.</p>
<p>If the SIgA antibodies in the nose, mouth or throat target SARS-CoV-2, they could neutralize the virus before it can drop down into the lungs and establish an infection.</p>
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<figcaption><span class="caption">Nasal vaccines could provide a more approachable alternative to injections for patients leery of needles.</span></figcaption>
</figure>
<h2>What advantage do mucosal vaccines have against COVID-19?</h2>
<p>I believe that arguably the best way to protect an individual against COVID-19 is to block the virus at its point of entry, or at least to confine it to the upper respiratory tract, where it might inflict relatively little damage.</p>
<p>Breaking chains of viral transmission is crucial to controlling epidemics. Researchers know that <a href="http://dx.doi.org/10.1093/cid/ciab691">COVID-19 spreads</a> during normal breathing and speech, and is exacerbated by sneezing, coughing, shouting, singing and other forms of exertion. Because these emissions mostly originate from saliva and nasal secretions, where the predominant form of antibody present is SIgA, it stands to reason that secretions with a sufficiently high level of SIgA antibodies against the virus could neutralize and thereby diminish its transmissibility.</p>
<p><a href="http://dx.doi.org/10.3389/fimmu.2022.957107">Existing vaccines</a>, however, do not induce SIgA antibody responses. Injected vaccines primarily induce circulating IgG antibodies, which are effective in preventing serious disease in the lungs. Nasal vaccines specifically induce SIgA antibodies in nasal and salivary secretions, where the virus is initially acquired, and can more effectively prevent transmission.</p>
<p>Nasal vaccines may be a useful supplement to injected vaccines in hot spots of infection. Since they don’t require needles, they might also help overcome vaccine hesitancy due to <a href="https://theconversation.com/over-half-of-adults-unvaccinated-for-covid-19-fear-needles-heres-whats-proven-to-help-161636">fear of injections</a>.</p>
<h2>How close are researchers to creating a nasal COVID-19 vaccine?</h2>
<p>There have been <a href="https://doi.org/10.1038/d41586-022-02824-3">over 100 oral or nasal COVID-19 vaccines in development</a> around the world.</p>
<p>Most of these have been or are currently being tested in animal models. <a href="http://dx.doi.org/10.1126/scitranslmed.abn6868">Many</a> <a href="http://dx.doi.org/10.1126/science.abo2523">have reported</a> successfully inducing protective antibodies in the blood and secretions, and have prevented infection in these animals. However, few have been successfully tested in people. Many <a href="https://www.pharmalive.com/altimmune-to-halt-trials-for-intranasal-covid-19-vaccine">have been abandoned</a> without fully reporting study details.</p>
<p>According to the <a href="https://www.who.int/publications/m/item/draft-landscape-of-covid-19-candidate-vaccines">World Health Organization</a>, 14 nasal COVID-19 vaccines are in clinical trials as of late 2022. Reports from <a href="https://doi.org/10.1038/d41586-022-02851-0">China and India</a> indicate that nasal or inhaled vaccines have been approved in these countries. But little information is publicly available about the results of the studies supporting approval of these vaccines.</p><img src="https://counter.theconversation.com/content/192567/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Michael W. Russell receives consultation fees from Therapyx, Inc., and has received previous research grants (now inactive) from the National Institutes of Health; he is also named on current grants to Therapyx, Inc. Therapyx has no interests in products for COVID-19.</span></em></p>An effective nasal vaccine could stop the virus that causes COVID-19 right at its point of entry. But devising one that works has been a challenge for researchers.Michael W. Russell, Professor Emeritus of Microbiology and Immunology, University at BuffaloLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1925702022-12-08T13:32:46Z2022-12-08T13:32:46ZPeople can have food sensitivities without noticeable symptoms – long-term consumption of food allergens may lead to behavior and mood changes<figure><img src="https://images.theconversation.com/files/499637/original/file-20221207-18-b6a7kw.jpg?ixlib=rb-1.1.0&rect=0%2C0%2C2121%2C1412&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Asymptomatic sensitization may lead people to continue consuming food allergens, causing hidden neurological issues.</span> <span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/photo/young-woman-in-striped-shirt-from-back-choosing-royalty-free-image/1357286617">Garetsworkshop/iStock via Getty Images Plus</a></span></figcaption></figure><p>The prevalence of food allergies is increasing worldwide, <a href="https://doi.org/10.1111/j.1399-3038.2011.01145.x">approaching an epidemic level</a> in some regions. In the U.S. alone, <a href="https://www.foodallergy.org/resources/facts-and-statistics">approximately 10% of children and adults</a> suffer from food allergies, with allergies to cow’s milk, eggs, peanuts and tree nuts being the most common. Some patients have mild symptoms that might not need medical attention, leaving these cases unreported. </p>
<p>Food allergies, or food hypersensitivities, result from the overreaction of the immune system to typically harmless proteins in food. They can manifest as a <a href="https://acaai.org/allergies/allergic-conditions/food/">spectrum of symptoms</a>, ranging from itching, redness and swelling for milder reactions, to vomiting, diarrhea, difficulty breathing and other potentially life-threatening symptoms for severe reactions.</p>
<p>Besides self-reporting, food allergies can be <a href="https://acaai.org/allergies/testing-diagnosis/">diagnosed by exposing patients</a> to trace amounts of offending proteins, or allergens, via their mouth or skin and observing their immediate reactions. More commonly, doctors use blood tests to measure the levels of <a href="https://www.aaaai.org/tools-for-the-public/allergy,-asthma-immunology-glossary/immunoglobulin-e-(ige)-defined">immunoglobulin E, or IgE</a>, a specialized antibody that the immune system uses to identify allergens and trigger a response. Although healthy individuals may have low levels of IgE in the blood, patients with food allergies have much higher levels that increase their risk of having severe allergic reactions.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/499636/original/file-20221207-16-gmhxjg.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="Patient undergoing skin-prick allergy test on arm" src="https://images.theconversation.com/files/499636/original/file-20221207-16-gmhxjg.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/499636/original/file-20221207-16-gmhxjg.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/499636/original/file-20221207-16-gmhxjg.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/499636/original/file-20221207-16-gmhxjg.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/499636/original/file-20221207-16-gmhxjg.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/499636/original/file-20221207-16-gmhxjg.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/499636/original/file-20221207-16-gmhxjg.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=503&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Skin-prick allergy tests involve exposing patients to trace amounts of an allergen and observing their reactions.</span>
<span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/photo/immunologist-doing-skin-prick-allergy-test-on-a-royalty-free-image/1288998568">ronstik/iStock via Getty Images</a></span>
</figcaption>
</figure>
<p>But <a href="https://doi.org/10.1159%2F000517824">some people</a> who test positive on skin-prick allergy tests with moderate increases in IgE don’t notice any allergy-related symptoms when they eat the allergen. This condition is sometimes referred to as <a href="https://www.verywellhealth.com/what-is-sensitization-82988">asymptomatic sensitization</a>. In many cases, people with this condition may not even be aware that they have a food hypersensitivity. </p>
<p>Are they truly asymptomatic, though? Or are there effects within their body that they aren’t aware of?</p>
<p>I am a <a href="https://scholar.google.com/citations?user=kXRRwk4AAAAJ&hl=en">neuroscientist</a> studying how the brain is affected by food allergies. I became interested in this topic when I found that some of my family members had a hypersensitivity to cow’s milk. Some totally avoid dairy products because they have experienced severe, life-threatening symptoms. Those who don’t have typical allergic reactions occasionally eat dairy, but appear to develop seemingly unrelated illnesses a day or two later.</p>
<p>What I and other researchers have found is that food allergens can affect your brain and behavior if you’re hypersensitized, even if you don’t have typical food allergy symptoms.</p>
<h2>Food allergies linked to behavioral disorders</h2>
<p>Researchers have suspected food hypersensitivities to be a potential cause for behavioral disorders for decades.</p>
<p>A <a href="https://doi.org/10.1097/00007611-194908000-00017">1949 case report</a> described behavioral and mood disturbances in patients after they ate certain foods, such as milk and eggs. Their symptoms improved after removing the suspected foods from their diet, suggesting that a food hypersensitivity was the likely culprit. However, I was intrigued that the patients had been able to eat the offending foods up until they chose to avoid them. In other words, they were asymptomatically sensitized, or tolerant, to the allergens.</p>
<p>Several recent studies in people have supported the association between food allergies and various neuropsychiatric disorders, including <a href="https://doi.org/10.1111/all.12829">depression, anxiety</a>, <a href="https://doi.org/10.1016/j.aller.2016.03.001">attention-deficit/hyperactivity disorder</a> and <a href="https://doi.org/10.1002/aur.2106">autism</a>. They strengthen the possibility that some reactions to food allergens could involve the nervous system and manifest as behavioral disorders.</p>
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<figcaption><span class="caption">The food you eat can affect your brain in many ways.</span></figcaption>
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<p>However, the idea of food hypersensitivity causing neuropsychiatric disorders is still controversial because of inconsistencies across studies. Differences in the types of allergies, ethnic backgrounds, dietary habits and other factors among the study participants can produce conflicting results. More importantly, some studies included those with self-reported food allergies, while others included only those with lab-confirmed food allergies. This limited investigations to only symptomatic individuals.</p>
<h2>Food hypersensitivity, brain and behavior</h2>
<p><a href="https://doi.org/10.1016/j.bbi.2021.03.002">My laboratory tested</a> whether food allergens could manifest as behavioral symptoms, particularly in asymptomatically sensitized individuals. We wanted to find out whether eating offending foods could lead to brain inflammation and behavioral changes after sensitization, even in the absence of other obvious severe reactions.</p>
<p>To minimize the individual differences found in human studies, we decided to work with mice. We sensitized mice of the same age and genetic background to the common milk allergen β-lactoglobulin, or BLG, and fed them the same diet in the same room. We found that while <a href="https://doi.org/10.1016/j.bbi.2021.03.002">BLG-sensitized mice</a> produced moderately but significantly elevated levels of IgE, they did not show immediate allergic reactions. They could even eat food containing the milk allergen for two weeks without showing any obvious symptoms, despite maintaining elevated levels of IgE. This indicated that they were asymptomatically sensitized.</p>
<p>We then observed whether they showed any changes in emotionally driven behavior. Because we could not ask mice how they felt, we deduced their “feelings” by noting changes from their normal, survival-oriented behavior. Mice instinctively explore their environment to search for food and shelter while avoiding potential danger. However, “anxious” mice tend to spend more time hiding to play it safe. We identified “depressed” mice by briefly holding them by the tail. Most mice will keep fighting to get out of the uncomfortable predicament, while depressed mice quickly give up.</p>
<p>Our experiments were designed to simulate situations where asymptomatically sensitized individuals would eat either a large amount of an offending food in one day or small amounts every day for a few weeks. We mimicked these situations by placing a large amount of the milk allergen directly into the stomach of sensitized mice with a feeding tube, or giving them an allergen-containing mouse chow to eat the allergen a little at a time.</p>
<p>Interestingly, BLG-sensitized mice showed <a href="https://doi.org/10.1016/j.bbi.2021.03.002">anxiety-like behavior</a> one day after receiving a large amount of the allergen. Another group of sensitized mice developed <a href="https://doi.org/10.3390/cells11040738">depression-like behavior</a> after eating small amounts of allergen for two weeks. In addition, BLG-sensitized mice showed signs of brain inflammation and neuronal damage, suggesting that changes in the brain may be responsible for their behavioral symptoms.</p>
<p>We also investigated the <a href="https://doi.org/10.3389/falgy.2022.870628">long-term effect</a> of allergen consumption by keeping BLG-sensitized mice on the allergen-containing diet for one month. We found that IgE levels declined in sensitized mice by the end of the month, indicating that continually eating small amounts of the allergen led to decreased immune responses, or “desensitization.” In contrast, signs of brain inflammation remained, suggesting that the harmful effect of allergens persisted in the brain.</p>
<h2>Chronic brain inflammation</h2>
<p>Researchers have yet to study prolonged brain inflammation, or neuroinflammation, in people who are asymptomatically sensitized. In general, though, <a href="https://doi.org/10.1172/JCI90609">chronic neuroinflammation</a> is a known contributor to neurodegenerative diseases, such as multiple sclerosis and Alzheimer’s disease, although the exact causes of these diseases are unknown. A better understanding of the role allergens play in neuroinflammation can help researchers clarify whether food allergens trigger chronic inflammation that can lead to these diseases.</p>
<p>This knowledge could be especially important for patients undergoing <a href="https://www.aaaai.org/Tools-for-the-Public/Allergy,-Asthma-Immunology-Glossary/Oral-Immunotherapy-Defined">oral immunotherapy</a>, an approach to allergy treatment that involves incrementally ingesting small amounts of allergens over time. The goal is to desensitize the immune system and reduce the incidence of anaphylaxis, or life-threatening allergic reactions. In 2020, the U.S. Food and Drug Administration <a href="https://www.fda.gov/news-events/press-announcements/fda-approves-first-drug-treatment-peanut-allergy-children">approved a standardized form of peanut allergens</a> to prevent anaphylaxis in eligible pediatric patients. However, its possible long-term effect on the nervous system is unknown.</p>
<p>Food allergens can affect the brain and behavior of seemingly asymptomatic people, making them not so asymptomatic neurologically. Considering how your brain responds to the food you eat puts a whole new meaning to the phrase “you are what you eat.”</p><img src="https://counter.theconversation.com/content/192570/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Kumi Nagamoto-Combs receives funding from the National Institute of Allergy and Infectious Disease and the National Institute on Aging. </span></em></p>Food allergies have been linked to behavioral and mood disorders, including depression, anxiety and ADHD.Kumi Nagamoto-Combs, Assistant Professor of Biomedical Sciences, University of North DakotaLicensed as Creative Commons – attribution, no derivatives.