Control of immediate hypersensitivity responses in parasitic and other diseases

National Institute Of Allergy And Infectious Diseases

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Abstract

The hygiene hypothesis suggests that parasitic infection modulates host immune responses and decreases atopy, but other data suggest parasitic infections may induce allergic responsiveness. To investigate the impact of molecular similarity among allergens and cross-reactive homologous helminth proteins IgE measurements in filarial-infected and noninfected individuals to allergen extracts that contained proteins with high levels of homology with helminth proteins as well as IgE against representative recombinant allergens with and without helminth homologs. Our data demonstrate that filarial infection was associated with IgE directed against house dust mite and cockroach, these having allergens with homologs in helminth infection. Mice infected with the helminth H.polygyrus also showed increased levels of IgE and positive skin tests to allergens with homologs in the parasite thereby demonstrating cross-reactivity among allergens and helminth proteins Control of allergic disease (and of parasitic helminth-associated pathology) is associated with decreased antigen-specific IgE and increased antigen-specific IgG4. Although IL-10 appears to contribute to altering the antigen-specific IgE: IgG4 ratio, how this occurs remains largely unknown. Using in vitro cultures of human PBMCs and B cell subsets we have demonstrated that IL-10 acts indirectly through accessory cells to downregulate IL-4-induced production of IgE. In contrast, IL-10 can act directly on B cells to upregulate IL-4-induced production of IgG4, with its effects downstream of germline transcription (Lin et al, unpublished).