title: Chitinase-like proteins promote IL-17-mediated neutrophilia in a tradeoff between nematode killing and host damage.
abstract: Enzymatically inactive chitinase-like proteins (CLPs) such as BRP-39, Ym1 and Ym2 are established markers of immune activation and pathology, yet their functions are essentially unknown. We found that Ym1 and Ym2 induced the accumulation of neutrophils through the expansion of γδ T cell populations that produced interleukin 17 (IL-17). While BRP-39 did not influence neutrophilia, it was required for IL-17 production in γδ T cells, which suggested that regulation of IL-17 is an inherent feature of mouse CLPs. Analysis of a nematode infection model, in which the parasite migrates through the lungs, revealed that the IL-17 and neutrophilic inflammation induced by Ym1 limited parasite survival but at the cost of enhanced lung injury. Our studies describe effector functions of CLPs consistent with innate host defense traits of the chitinase family.
authors.affiliation: Institute of Immunology and Infection Research, Centre for Immunity Infection and Evolution, School of Biological Sciences, University of Edinburgh, Edinburgh, UK.
authors.forename: Tara E
authors.initials: TE
authors.lastname: Sutherland
authors.affiliation: Institute of Immunology and Infection Research, Centre for Immunity Infection and Evolution, School of Biological Sciences, University of Edinburgh, Edinburgh, UK.
authors.forename: Nicola
authors.initials: N
authors.lastname: Logan
authors.affiliation: Institute of Immunology and Infection Research, Centre for Immunity Infection and Evolution, School of Biological Sciences, University of Edinburgh, Edinburgh, UK.
authors.forename: Dominik
authors.initials: D
authors.lastname: Rückerl
authors.affiliation: Department of Respiratory, Inflammation &Autoimmunity, MedImmune, Gaithersburg, Maryland, USA.
authors.forename: Alison A
authors.initials: AA
authors.lastname: Humbles
authors.affiliation: Faculty of Life Sciences, University of Manchester, Manchester, UK.
authors.forename: Stuart M
authors.initials: SM
authors.lastname: Allan
authors.affiliation: Division of Molecular Immunology, Medical Research Council National Institute for Medical Research, London, UK.
authors.forename: Venizelos
authors.initials: V
authors.lastname: Papayannopoulos
authors.affiliation: Division of Molecular Immunology, Medical Research Council National Institute for Medical Research, London, UK.
authors.forename: Brigitta
authors.initials: B
authors.lastname: Stockinger
authors.affiliation: Institute of Immunology and Infection Research, Centre for Immunity Infection and Evolution, School of Biological Sciences, University of Edinburgh, Edinburgh, UK.
authors.forename: Rick M
authors.initials: RM
authors.lastname: Maizels
authors.affiliation: Institute of Immunology and Infection Research, Centre for Immunity Infection and Evolution, School of Biological Sciences, University of Edinburgh, Edinburgh, UK.
authors.forename: Judith E
authors.identifier: 000000023829066X
authors.initials: JE
authors.lastname: Allen
mesh_terms: D000818:Animals; D000071451:Chitinase-3-Like Protein 1; D002688:Chitinases / Q000276:immunology*; D003602:Cytotoxicity, Immunologic / Q000276:immunology; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D006023:Glycoproteins / Q000276:immunology*; D007113:Immunity, Innate / Q000276:immunology; D007249:Inflammation / Q000276:immunology; D020381:Interleukin-17 / Q000276:immunology; D037102:Lectins / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009348:Nematoda; D009349:Nematode Infections / Q000276:immunology*; D020556:Neutrophil Infiltration / Q000276:immunology*; D009504:Neutrophils / Q000276:immunology; D060888:Real-Time Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000276:immunology; D014162:Transfection; D001619:beta-N-Acetylhexosaminidases / Q000276:immunology*
chemical_list: C509289:Chil1 protein, mouse; D000071451:Chitinase-3-Like Protein 1; D006023:Glycoproteins; D020381:Interleukin-17; D037102:Lectins; D002688:Chitinases; C525260:Ym2 protein, mouse; C429541:Chil3 protein, mouse; D001619:beta-N-Acetylhexosaminidases