The Hygiene Hypothesis and Immunity to Parasitic Helminths

Abstract

The hygiene hypothesis proposes that exposure to microorganisms might alter the immune system such that allergic diseases that are mediated by Th2 type responses no longer can develop. The immunological explanation of the hygiene hypothesis is rooted in the notion that a decrease in exposure to pathogens would weaken the Th1 type immune responses and therefore allow proallergic Th2 responses to become dominant. Helminth infections are a class of infectious agents that are highly prevalent in developing countries and currently affect more than two billion people worldwide in the same areas where the prevalence of allergies is low. As helminth infections induce a strong Th2 response, the immunological explanation of the hygiene hypothesis does not hold as in the same areas where Th2-inducing helminth infections are rampant, allergic disorders are seldom seen. There are currently two explanations for the inverse relationship between helminths and allergies despite both diseases being associated with Th2 responses. One is that chronic helminth infections are associated with strong regulatory responses which encompass regulatory T cells, regulatory B cells, alternatively activated macrophages, and tolerogenic dendritic cells and, therefore, can dampen inflammatory reactions. The other is that IgE responses that are induced in the presence of helminth infections are often to cross-reactive carbohydrate epitopes which have poor biological activity and therefore do not lead to allergic reactions. Insight into these two mechanisms can provide us with potential new treatments for allergic diseases using analogues of helminth-derived molecules.