1. Helminth infection protects mice from anaphylaxis via IL-10-producing B cells.
- Author
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Mangan NE, Fallon RE, Smith P, van Rooijen N, McKenzie AN, and Fallon PG
- Subjects
- Adoptive Transfer, Anaphylaxis genetics, Anaphylaxis parasitology, Animals, Antigens, Differentiation biosynthesis, B-Lymphocyte Subsets parasitology, B-Lymphocyte Subsets transplantation, Cells, Cultured, Cytokines deficiency, Cytokines genetics, Female, Genetic Predisposition to Disease, Host-Parasite Interactions, Immunity, Innate, Immunization, Passive, Interleukin-10 pharmacology, Interleukin-10 physiology, Interleukin-4 pharmacology, Macrophage-1 Antigen biosynthesis, Macrophages immunology, Macrophages metabolism, Male, Mice, Mice, Inbred BALB C, Mice, Inbred C57BL, Mice, Inbred CBA, Mice, Knockout, Penicillin V administration & dosage, Penicillin V immunology, Platelet Activating Factor administration & dosage, Receptors, Interleukin-2 biosynthesis, Schistosomiasis mansoni genetics, Schistosomiasis mansoni parasitology, T-Lymphocyte Subsets immunology, T-Lymphocyte Subsets metabolism, Th2 Cells immunology, Th2 Cells metabolism, Up-Regulation immunology, Anaphylaxis immunology, Anaphylaxis prevention & control, B-Lymphocyte Subsets immunology, B-Lymphocyte Subsets metabolism, Interleukin-10 biosynthesis, Schistosomiasis mansoni immunology
- Abstract
Modulation of the immune system by infection with helminth parasites, including schistosomes, is proposed to reduce the levels of allergic responses in infected individuals. In this study we investigated whether experimental infection with Schistosoma mansoni could alter the susceptibility of mice to an extreme allergic response, anaphylaxis. We formally demonstrate that S. mansoni infection protects mice from an experimental model of systemic fatal anaphylaxis. The worm stage of infection is shown to mediate this protective effect. In vivo depletion studies demonstrated an imperative role for B cells and IL-10 in worm-mediated protection. Furthermore, worm infection of mice increases the frequency of IL-10-producing B cells compared with that in uninfected mice. However, transfer of B cells from worm-infected mice or in vitro worm-modulated B cells to sensitized recipients exacerbated anaphylaxis, which was attributed to the presence of elevated levels of IL-4-producing B cells. Worm-modulated, IL-10-producing B cells from IL-4-deficient, but not IL-5-, IL-9- or IL-13-deficient, mice conferred complete resistance to anaphylaxis when transferred to naive mice. Therefore, we have dissected a novel immunomodulatory mechanism induced by S. mansoni worms that is dependent on an IL-10-producing B cell population that can protect against allergic hypersensitivity. These data support a role for helminth immune modulation in the hygiene hypothesis and further illustrate the delicate balance between parasite induction of protective regulatory (IL-10) responses and detrimental (IL-4) allergic responses. more...
- Published
- 2004
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