title: Helminth Products Protect against Autoimmunity via Innate Type 2 Cytokines IL-5 and IL-33, Which Promote Eosinophilia.
abstract: Epidemiologic studies in humans have demonstrated that infection with helminth parasites is associated with a reduced risk of developing autoimmune diseases. Mechanistic studies in mice have linked the protective effect of helminths on autoimmunity to the suppressive activity of helminth-induced regulatory T cells (Tregs) or Th2 cells. In this study, we demonstrate that treatment of mice with Fasciola hepatica excretory-secretory products (FHES) attenuated the clinical signs of experimental autoimmune encephalomyelitis (EAE), a mouse model of multiple sclerosis. Protection was associated with a significant reduction in the infiltration of pathogenic Th1 and Th17 cells into the brain. Although FHES enhanced anti-inflammatory cytokine and Th2 responses, protection against EAE was independent of IL-4, IL-10, and Tregs. However, administration of FHES induced production of the type 2 cytokines IL-33 and IL-5, which promoted accumulation of eosinophils. FHES-induced expansion of eosinophils and protection against EAE was lost in IL-33(-/-) mice and upon neutralization of IL-5. Furthermore, transfer of FHES-induced or IL-33-induced eosinophils conferred protection against EAE. In addition, treatment of mice with recombinant IL-33 attenuated autoimmunity, and this was dependent on IL-5. To our knowledge, this study is the first to report a role for helminth-induced IL-5 and IL-33 in protection against autoimmunity.
authors.affiliation: Immune Regulation Research Group, School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin 2, Ireland;
authors.forename: Conor M
authors.identifier: http://orcid.org/0000-0001-8285-0903
authors.initials: CM
authors.lastname: Finlay
authors.affiliation: Immune Regulation Research Group, School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin 2, Ireland;
authors.forename: Anna M
authors.initials: AM
authors.lastname: Stefanska
authors.affiliation: Immune Regulation Research Group, School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin 2, Ireland;
authors.forename: Kevin P
authors.initials: KP
authors.lastname: Walsh
authors.affiliation: Immune Regulation Research Group, School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin 2, Ireland;
authors.forename: Patrick J
authors.initials: PJ
authors.lastname: Kelly
authors.affiliation: EPIRUS Biopharmaceuticals Netherlands BV, 3584 CM Utrecht, the Netherlands;
authors.forename: Louis
authors.initials: L
authors.lastname: Boon
authors.affiliation: Adjuvant Research Group, School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin 2, Ireland; and.
authors.forename: Ed C
authors.initials: EC
authors.lastname: Lavelle
authors.affiliation: Tolerance and Autoimmunity Research Group, Department of Clinical Medicine, School of Medicine, Trinity College Dublin, Dublin 2, Ireland.
authors.forename: Patrick T
authors.identifier: http://orcid.org/0000-0002-0130-8766
authors.initials: PT
authors.lastname: Walsh
authors.affiliation: Immune Regulation Research Group, School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin 2, Ireland; kingston.mills@tcd.ie.
authors.forename: Kingston H G
authors.initials: KH
authors.lastname: Mills
mesh_terms: D000818:Animals; D000947:Antigens, Helminth / Q000276:immunology*; D015551:Autoimmunity / Q000276:immunology*; D004195:Disease Models, Animal; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D004802:Eosinophilia / Q000276:immunology*; D005434:Flow Cytometry; D007113:Immunity, Innate / Q000276:immunology; D000067596:Interleukin-33 / Q000276:immunology*; D015848:Interleukin-5 / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018418:Th2 Cells / Q000276:immunology*
chemical_list: D000947:Antigens, Helminth; C506535:Il33 protein, mouse; D000067596:Interleukin-33; D015848:Interleukin-5