I cut my teeth on allergy and asthma. For my M.S., I worked in a lab that looked at hypersensitivity to Aspergillus fumigatus, a pretty common mold whose star has risen as a potential invasive/infectious disease biggie in our largely immunosuppressed world. My work concentrated on the allergenic prowess of A.fumigatus, however, and I looked more at systemic pathology rather than any particular cell-type or mediator. Of course, pathology in allergic disease is under the control of many cell types and their assorted secreted nasties, and those, in turn, are directed by cytokines secreted by CD4+ T-cells.
Now, an allergy is a propensity to an inappropriate, aberrant immune response to something that doesn’t quite warrant it. Peanuts, dander and pollen are meant to be enjoyed, brushed away…and, gee, I don’t know what one does with pollen…In allergic individuals, however, these seemingly innocuous antigens elicit a strong, inflammatory immune response, characterised by high titers of IgE, eosinophilia and the presence of hallmark Th2 cytokines like IL-4, IL-5, IL-13, IL-33, SCF and TSLP. Given that Th2 refers to a type of T-helper (type 2, specifically) response, one has to wonder why the usually on-point, meticulous T-cell has such an overreaction to Elizabeth Barrett Browning’s (which is what I would name my cat) dander.
The Hygiene Hypothesis offers an explanation. My understanding of this is that a clean, sanitary lifestyle somehow predisposes the immune system to act out against a non-immunostimulatory antigen. Now immune systems that develop in unsanitary strife of a variety of irritants and potential pathogens learn quickly to deal, and respond only to potentially problematic antigens.
However, the Extended Hygiene Hypothesis takes a larger picture view of the same idea wherein it claims that the composition of gut microbes in children as well childhood infections to worms, for example, eventually influence the inflammatory response. This becomes important because it is the prevalence of chronic inflammation that unites the ostensibly different disorders of allergic asthma, atopic dermatitis, type 2 diabetes and, wait for it, depression. The Extended Hygiene Hypothesis states that early exposure to a more diverse microbial population will bring forth a worldlier immune system that shall not freak out any time the status quo is changed, thus, less allergies, and inflammation that does not overstay its welcome.
A vote in support of the above is seen in da Costa et al’s study “Schistosoma mansoni-Mediated Suppression of Allergic Airway Inflammation Requires Patency and Foxp3+ Treg Cells” published in PLoS Neglected Tropical Diseases on August 15th, 2013. The study is strong proof for the Bystander Suppression phenomenon wherein the immune response to worm antigens suppresses the similar immune response made to OVA allergen. This, to me, is a powerful observation since it gives us a glimpse into the “priorities” of the immune system, as it were. The immune system goes back to basics when faced with both an allergen and a pathogen: after all, the Th2 response evolved to deal with metazoan parasites.
Further, the authors also uncover a new putative mechanism by which suppression of airway inflammation is mediated: via T-reg cells. Foxp3+ve, CD4+ve T-cells, or regulatory T-cells are the effective voice of reason during inflammation, the voice that goes, “Shut it down!” to cells that are cranking out inflammatory factors with wild abandon. Obvious as this may seem now, as da Costa et al say, the silencing of airway inflammation has, classically, been the prerogative of regulatory B-cells and that eternal pacifist, IL-10.
So, is the worm the answer? Is it the intermediary that needs to be reintroduced into the equation so that different T-cell populations can talk and abrogate allergic inflammation? Apparently, this is a thing. It’s not as unorthodox if it sounds if research manages to unearth immunostimulatory components from worms that act as the Rosetta Stone of cytokinic communication between cell types and, ultimately, reduce allergy altogether. Could we be headed towards an age where any child who yearns for a pet is reminded that s/he bears a symbiont worm within?
Stranger things have happened. 🙂
Take care now,