title: IL-33, a potent inducer of adaptive immunity to intestinal nematodes.
abstract: IL-33 (IL-1F11) binds ST2 (IL-1R4), both of which are associated with optimal CD4(+) Th2 polarization. Exogenous IL-33 drives induction of Th2-associated cytokines and associated pathological changes within the gut mucosa. Th2 polarization is also a prerequisite to expulsion of the intestinal-dwelling nematode Trichuris muris. In this study, we demonstrate that IL-33 mRNA is expressed early during parasite infection and susceptible mice can be induced to expel the parasite by a regime of exogenous IL-33 administration. IL-33 prevents an inappropriate parasite-specific Th1-polarized response and induces IL-4, IL-9, and IL-13. This redirection requires the presence of T cells and must occur at the initiation of the response to the pathogen. Interestingly, exogenous IL-33 also induced thymic stromal lymphopoietin mRNA within the infected caecum, an epithelial cell-restricted cytokine essential for the generation of Th2-driven parasite immunity. IL-33 also acts independently of T cells, altering intestinal pathology in chronically infected SCID mice, leading to an increased crypt length and intestinal epithelial cell proliferation, but reducing goblet cell hyperplasia. Thus, the ability of IL-33 to induce Th2 responses has functional relevance in the context of intestinal helminth infection, particularly during the initiation of the response.
authors.affiliation: Faculty of Life Sciences, University of Manchester, Oxford Road, Manchester, United Kingdom.
authors.forename: Neil E
authors.initials: NE
authors.lastname: Humphreys
authors.forename: Damo
authors.initials: D
authors.lastname: Xu
authors.forename: Matthew R
authors.initials: MR
authors.lastname: Hepworth
authors.forename: Foo Y
authors.initials: FY
authors.lastname: Liew
authors.forename: Richard K
authors.initials: RK
authors.lastname: Grencis
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D006801:Humans; D007111:Immunity, Cellular / Q000235:genetics; D007113:Immunity, Innate / Q000235:genetics; D000067596:Interleukin-33; D007378:Interleukins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology* / Q000627:therapeutic use*; D007411:Intestinal Diseases, Parasitic / Q000276:immunology* / Q000473:pathology / Q000517:prevention & control; D051379:Mice; D008806:Mice, Inbred AKR; D008807:Mice, Inbred BALB C; D016513:Mice, SCID; D012333:RNA, Messenger / Q000096:biosynthesis; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000096:biosynthesis / Q000235:genetics / Q000627:therapeutic use; D014257:Trichuriasis / Q000276:immunology* / Q000473:pathology / Q000517:prevention & control; D014258:Trichuris / Q000276:immunology*
chemical_list: C506535:Il33 protein, mouse; D000067596:Interleukin-33; D007378:Interleukins; D012333:RNA, Messenger; D011994:Recombinant Proteins