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The Potential Impact of Early Exposures to Geohelminth Infections on the Development of Atopy

Abstract:

Microbial exposures in early life may provide important signals for immune maturation and the development of an antiinflammatory network thereby preventing the development of dysregulated immune responses such as that associated with allergic disease. The human immune system has evolved in the presence of intense helminth infections and has developed regulatory mechanisms to limit the harmful inflammation that can be caused by the potent allergens secreted by these chronic pathogens. Geohelminth infections are highly prevalent childhood infections, and there is strong evidence that chronic geohelminth infections provide protection against atopy in the rural tropics. Because the early environmental exposures that may lead to the development of atopy are likely to occur in the first few years of life, geohelminth infections may exert their protective effects at this time. Early exposures to geohelminth antigens could occur transplacentally, through breast milk, or through early infant exposures, and could induce tolerance to parasite antigens resulting in suppressed allergic responses to the parasite. Tolerization to parasite antigens could suppress allergic responses to inhalant allergens through bystander effects or through tolerization of crossreactive epitopes that are shared between geohelminth parasites and inhalant allergens. Tolerization to crossreactive allergens could occur by thymic deletion or through peripheral mechanisms such as regulatory T cells. Immunologic studies of the mechanisms by which early exposures to geohelminth infections affect immune polarization to inhalant allergens are likely to provide important insights into the early regulation of the immune response and may lead to the design of novel interventions for the prevention of allergic disease.