By Amanda Keener
If you have allergies, it may be because you don’t have worms. At least, that is, according to the “hygiene hypothesis” and its more recent cousin, the “old friends hypothesis.” Both of these suggest that the absence of pathogens and microorganisms in our environment somehow promotes atopic allergic diseases and are supported by the rise of allergies in Western cultures throughout the 20th century. The “old friends hypothesis” suggests that the type of microorganisms we come in contact with matter; those that humans as a population have grown accustomed to offer benefits that are lost as sanitation increases. Tiny worm-like parasites called helminthes have been the case-in-point for this idea. Helminth infection can re-program the immune response by promoting the production of regulatory T cells and B cells. These cells balance their inflammatory counterparts and the worms create an environment for themselves where the immune system is dulled and incapable of clearing the invaders.
Epidemiologically, helminth infection is inversely related to allergic and autoimmune diseases. Some studies, however, have found that helminthes actually aggravate allergies. In a recent issue of PLoS Neglected Tropical Diseases, Layland et al took a closer look at this relationship in mice. They used the blood fluke, Schistosoma mansoni to ask whether the stage of the parasitic infection would influence how the immune response responded to allergic airway inflammation.
They infected mice with S. mansoni and during different stages of the parasite’s life cycle, they sensitized the mice to egg ovalbumin, a protein commonly used for studying antigen-specific immune cells. Repeated exposures to the OVA essentially make the mice allergic to it, so that when they are challenged with the aerosolized protein many weeks late, they get an allergic airway inflammatory response, much like asthma. If the mice were sensitized to the allergen during the time that the parasites were actively producing eggs, then the immune response to the allergen was significantly reduced. This protection against lung inflammation was absent if sensitization to the allergen took place during the early stages of infection.
To understand how the egg-producing stage of the infection prevented airway inflammation, the researchers looked to the regulatory T cell (Treg) population, which had been known to expand during helminth infection. The late stage infected mice did in fact have greater numbers of Tregs in the lymph nodes draining the lungs. If the researchers depleted the Tregs during the allergen sensitization, the mice responded to OVA challenge with lung inflammation whether or not they were infected with the parasite. So, the Tregs were vital in mediating the anti-allergic effect of the S. mansoni eggs.
It would be interesting to know how the Treg population changed during the course of the infection—were they only expanded during the late, egg-producing stage and not the earlier stages? The group didn’t compare the cellular immune responses of the mice sensitized during early and late stage infection, so it’s unclear whether eggs direct better Treg expansion than worms. What is clear is that the stage the helminth infection is at during allergen sensitization does matter and this study may help explain the variability in the way that helminthes direct allergic responses. It may also direct researchers to potentially useful antigens expressed only by the eggs that could be explored as therapies to treat or prevent allergies.
Amanda Keener is a freelance science writer and a PhD candidate in Microbiology and Immunology. She writes about immunology research on her blog ImmYOUnology.