Eosinophils are required to suppress Th2 responses in Peyer's patches during intestinal infection by nematodes.
Infections with enteric nematodes result in systemic type 2 helper T (Th2) responses, expansion of immunoglobulin (Ig)G1 antibodies, and eosinophilia. Eosinophils have a supportive role in mucosal Th2 induction during airway hyperreactivity. Whether eosinophils affect the local T-cell and antibody response in the gut-associated lymphoid tissue during enteric infections is unknown. We infected eosinophil-deficient ΔdblGATA-1 mice with the Th2-inducing small intestinal nematode Heligmosomoides polygyrus and found that parasite fecundity was decreased in the absence of eosinophils. A lack of eosinophils resulted in significantly augmented expression of GATA-3 and IL-4 by CD4+T cells during acute infection, a finding strictly limited to Peyer's patches (PP). The increase in IL-4-producing cells in ΔdblGATA-1 mice was particularly evident within the CXCR5+PD-1+T-follicular helper cell population and was associated with a switch of germinal centre B cells to IgG1 production and elevated serum IgG1 levels. In contrast, infected wild-type mice had a modest IgG1 response in the PP, whereas successfully maintaining a population of IgA+germinal center B cells. Our results suggest a novel role for eosinophils during intestinal infection whereby they restrict IL-4 responses by follicular T helper cells and IgG1 class switching in the PP to ensure maintenance of local IgA production.
Institute of Immunology, Department of Veterinary Medicine, Freie Universität Berlin, Berlin, Germany.
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Strandmark
Institute of Immunology, Department of Veterinary Medicine, Freie Universität Berlin, Berlin, Germany.
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Steinfelder
Deutsches Rheuma Forschungszentrum Berlin, a Leibniz Institute, Berlin, Germany.
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Berek
Department of Internal Medicine, Rheumatology and Clinical Immunology/Research Center ImmunoSciences (RCIS), Charité-University Medicine Berlin, Berlin, Germany.
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Kühl
Institute of Immunology, Department of Veterinary Medicine, Freie Universität Berlin, Berlin, Germany.
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Rausch
Institute of Immunology, Department of Veterinary Medicine, Freie Universität Berlin, Berlin, Germany.
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Hartmann
D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology*; D002478:Cells, Cultured; D004804:Eosinophils / Q000276:immunology* / Q000469:parasitology; D005260:Female; D050990:GATA3 Transcription Factor / Q000235:genetics / Q000378:metabolism; D007108:Immune Tolerance; D007070:Immunoglobulin A / Q000378:metabolism; D007074:Immunoglobulin G / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D007422:Intestines / Q000276:immunology* / Q000469:parasitology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009351:Nematospiroides dubius / Q000276:immunology*; D010581:Peyer's Patches / Q000276:immunology*; D017206:Strongylida Infections / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology*
D050990:GATA3 Transcription Factor; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D015847:Interleukin-4