Altered Responses to Food Proteins in Enteric Infections

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DESCRIPTION (provided by applicant): Infection with an enteric parasite can act as an adjuvant to prime for a Th2 biased response to a typically tolerogenic form of dietary antigen. However, in agreement with recent clinical and epidemiological studies, we have found that helminth infection protects against the anaphylactic symptoms and antigen specific IgE induced in a model of food allergy. Helminth dependent protection against allergy was abrogated when helminth infected, allergen sensitized mice were treated with neutralizing antibodies to IL-10. The unexpected identification of Th2 responses without atopy has led to the suggestion that helminth infection induces a specialized subset of dendritic cells that drive the generation of immunoregulatory T cells. Our data provide the basis for an ideal experimental model in which to test this hypothesis, hi Aim 1 we will examine whether helminth-induced protection against allergy is attributable to IL-10 secreting T cells. Helminth infection may also influence allergen presentation directly, via its effects on antigen presenting cells. This possibility is explored in Aim 2. The impaired responsiveness to oral vaccines observed in helminth-infected individuals may also be a consequence of helminth-induced immunosuppression. Characterization of the mechanisms by which infection influences the response to oral vaccines, as proposed in Aim 3 has practical implications for maximizing vaccine efficacy in the developing world. The induction of immunoregulatory mediators by chronic enteric infection is not likely to be restricted to helminth infection but may be a feature common to all types of infection that serves to maximize protective immunity while minimizing pathology.