Helminth infection protects mice from anaphylaxis via IL-10-producing B cells.
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.
Mangan
Niamh E
NE
Department of Biochemistry, Trinity College, Dublin, Ireland.
Fallon
Rosemary E
RE
Smith
Philip
P
van Rooijen
Nico
N
McKenzie
Andrew N
AN
Fallon
Padraic G
PG
D019264:Adoptive Transfer; D000707:Anaphylaxis / Q000235:genetics / Q000276:immunology* / Q000469:parasitology / Q000517:prevention & control*; D000818:Animals; D000943:Antigens, Differentiation / Q000096:biosynthesis; D016175:B-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism* / Q000469:parasitology / Q000637:transplantation; D002478:Cells, Cultured; D016207:Cytokines / Q000172:deficiency / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease; D006790:Host-Parasite Interactions; D007113:Immunity, Innate; D007116:Immunization, Passive; D016753:Interleukin-10 / Q000096:biosynthesis* / Q000494:pharmacology / Q000502:physiology; D015847:Interleukin-4 / Q000494:pharmacology; D016177:Macrophage-1 Antigen / Q000096:biosynthesis; D008264:Macrophages / Q000276:immunology / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D018345:Mice, Knockout; D010404:Penicillin V / Q000008:administration & dosage / Q000276:immunology; D010972:Platelet Activating Factor / Q000008:administration & dosage; D015375:Receptors, Interleukin-2 / Q000096:biosynthesis; D012555:Schistosomiasis mansoni / Q000235:genetics / Q000276:immunology* / Q000469:parasitology; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism; D018418:Th2 Cells / Q000276:immunology / Q000378:metabolism; D015854:Up-Regulation / Q000276:immunology
D000943:Antigens, Differentiation; D016207:Cytokines; D016177:Macrophage-1 Antigen; D010972:Platelet Activating Factor; D015375:Receptors, Interleukin-2; C036763:monocyte-macrophage differentiation antigen; D016753:Interleukin-10; D015847:Interleukin-4; D010404:Penicillin V