Allergic reactions don’t seem to benefit people, so why do so many of us have them? What is the evolutionary advantage? The answer, as it happens, may lie in parasitic worms.
The way our body’s immune system responds to allergens is very similar to the way it responds to parasitic worm (helminth) infections, and a recent study showed that molecules of plant allergens do indeed bear a striking resemblance to molecules encoded in the genomes of helminths. For example, an allergen found in birch pollen that is responsible for many allergic symptoms in early spring, mimics a protein found in the parasitic worm that causes bilharzia, a tropical disease caused by parasitic worms. This protein was found to be causing an allergic type of response in Ugandans who were exposed to the worm.
The existence of similar structures in helminths and plants is not in itself surprising. All life forms are constructed from the same building blocks. For example, about two-thirds of human genes originate from the earliest life forms on Earth: microscopic organisms like bacteria, archaea and eukaryotes.
Estimates for how many genes are shared between helminths and plants are likely to be similar. But there is clearly something special about molecules that trigger an allergic-type response, and these new findings might get us closer to understanding what this is, and help us to develop new treatments for hay fever and asthma.
Balancing the energy budget
But why, in the modern world, where parasitic worm infections are rare, are these anti-helminth mechanisms so active? One view is that in the absence of helminths, the helminth-fighting arm of the immune system turns up its sensitivity in order to seek the target for which it evolved, and instead accidentally targets similar, but harmless, substances in the natural environment. But there is a weakness in this argument.
The immune system uses large quantities of energy. Developmental biologists now talk about the central role of energy budgeting in evolution. If too much energy is consumed by the immune system there is less available for growth, maintenance and repair. In evolving humans that were struggling for adequate nutrition, allowing the immune system to waste energy would have had serious consequences. If helminths are absent, the relevant immune mechanisms should go into standby mode, not overdrive.
The answer lies in another area of evolutionary biology where helminths can be considered as “old infections”. These old infections evolved the ability to persist in our ancestors’ small hunter-gatherer groups. Once helminths are established the immune system can’t get rid of them, and attempts to do so merely waste energy and damage the host. So, in order to persist without endangering the host, helminths partially suppress the host’s immune response. This suppression blocks inflammation-induced complications such as elephantiasis, which would be bad news for both worm and host.
To regulate the immune system some helminths release molecules that increase the numbers of regulatory lymphocytes – which suppress inappropriate immune responses – and so act as the peacekeepers of the immune system. Other helminths change the behaviour of the cells that initiate the immune response so that it regulates rather than attacks. Still others enhance gut microorganisms that help to reduce inflammation.
We know from animal experiments and a few preliminary studies in humans that helminths can inhibit not just allergies, but also other chronic inflammatory disorders that are increasing in parallel with allergies, such as multiple sclerosis, type 1 diabetes and Crohn’s disease.
Helminths calm the immune system, then, but not only those mechanisms used by the immune system in allergic responses. They calm entirely different mechanisms involved in the other chronic inflammatory disorders too. When it comes to helminths, there is a lot going on.
Should we eat worms?
So could it be that the immune system evolved to anticipate the continued presence of helminths, and that in order to calm the immune system we should all carry a harmless load of worms, perhaps given at birth? That is what some people believe, and clinical trials looking into whether this will work are underway for several chronic inflammatory disorders. But this all depends on whether the requirement for helminths is genetically encoded in our DNA, because of our evolutionary past, or whether it only occurs if helminths are present during our growth and development.
If a need for helminths is encoded in our DNA sequences, then we might indeed need us to carry helminths, or at least learn to devise drugs that exploit the molecular tricks that helminths use to regulate our immune system. On the other hand, perhaps it is only when helminths are present during pregnancy and early life that our immune system “assumes” they will persist and will take responsibility for essential regulatory duties. If this is correct, then after a few generations without helminths, immune systems that have developed in the absence of these worms might lose this requirement. But we will still need the studies to prove it.