title: Eosinophil-derived IL-10 supports chronic nematode infection.
abstract: Eosinophilia is a feature of the host immune response that distinguishes parasitic worms from other pathogens, yet a discrete function for eosinophils in worm infection has been elusive. The aim of this study was to clarify the mechanism(s) underlying the striking and unexpected observation that eosinophils protect intracellular, muscle-stage Trichinella spiralis larvae against NO-mediated killing. Our findings indicate that eosinophils are specifically recruited to sites of infection at the earliest stage of muscle infection, consistent with a local response to injury. Early recruitment is essential for larval survival. By producing IL-10 at the initiation of infection, eosinophils expand IL-10(+) myeloid dendritic cells and CD4(+) IL-10(+) T lymphocytes that inhibit inducible NO synthase (iNOS) expression and protect intracellular larvae. The results document a novel immunoregulatory function of eosinophils in helminth infection, in which eosinophil-derived IL-10 drives immune responses that eventually limit local NO production. In this way, the parasite co-opts an immune response in a way that enhances its own survival.
authors.affiliation: Baker Institute for Animal Health, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853;
authors.forename: Lu
authors.initials: L
authors.lastname: Huang
authors.affiliation: Baker Institute for Animal Health, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853;
authors.forename: Nebiat G
authors.initials: NG
authors.lastname: Gebreselassie
authors.affiliation: Baker Institute for Animal Health, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853;
authors.forename: Lucille F
authors.initials: LF
authors.lastname: Gagliardo
authors.affiliation: Baker Institute for Animal Health, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853;
authors.forename: Maura C
authors.initials: MC
authors.lastname: Ruyechan
authors.affiliation: Division of Hematology/Oncology, Department of Biochemistry and Molecular Biology, Mayo Clinic Arizona, Scottsdale, AZ 85259; and.
authors.forename: Nancy A
authors.initials: NA
authors.lastname: Lee
authors.affiliation: Division of Pulmonary Medicine, Department of Biochemistry and Molecular Biology, Mayo Clinic Arizona, Scottsdale, AZ 85259.
authors.forename: James J
authors.initials: JJ
authors.lastname: Lee
authors.affiliation: Baker Institute for Animal Health, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853; jaa2@cornell.edu.
authors.forename: Judith A
authors.initials: JA
authors.lastname: Appleton
mesh_terms: D000818:Animals; D001119:Arginase / Q000235:genetics / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D049109:Cell Proliferation; D002908:Chronic Disease; D003713:Dendritic Cells / Q000276:immunology; D004802:Eosinophilia / Q000276:immunology; D004804:Eosinophils / Q000276:immunology*; D016753:Interleukin-10 / Q000096:biosynthesis / Q000276:immunology*; D007958:Leukocyte Count; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009569:Nitric Oxide / Q000096:biosynthesis*; D052247:Nitric Oxide Synthase Type II / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D051381:Rats; D017160:Trichinella spiralis / Q000276:immunology*; D014235:Trichinellosis / Q000276:immunology*
chemical_list: C556062:IL10 protein, mouse; D016753:Interleukin-10; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II; D001119:Arginase