title: Acidic chitinase primes the protective immune response to gastrointestinal nematodes.
abstract: Acidic mammalian chitinase (AMCase) is known to be induced by allergens and helminths, yet its role in immunity is unclear. Using AMCase-deficient mice, we show that AMCase deficiency reduced the number of group 2 innate lymphoid cells during allergen challenge but was not required for establishment of type 2 inflammation in the lung in response to allergens or helminths. In contrast, AMCase-deficient mice showed a profound defect in type 2 immunity following infection with the chitin-containing gastrointestinal nematodes Nippostrongylus brasiliensis and Heligmosomoides polygyrus bakeri. The impaired immunity was associated with reduced mucus production and decreased intestinal expression of the signature type 2 response genes Il13, Chil3, Retnlb, and Clca1. CD103(+) dendritic cells, which regulate T cell homing, were also reduced in mesenteric lymph nodes of infected AMCase-deficient mice. Thus, AMCase functions as a critical initiator of protective type 2 responses to intestinal nematodes but is largely dispensable for allergic responses in the lung.
authors.affiliation: Program in Tissue Immunity and Repair, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: Kevin M
authors.identifier: http://orcid.org/0000-0002-0972-5011
authors.initials: KM
authors.lastname: Vannella
authors.affiliation: Program in Tissue Immunity and Repair, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: Thirumalai R
authors.initials: TR
authors.lastname: Ramalingam
authors.affiliation: Program in Tissue Immunity and Repair, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: Kevin M
authors.initials: KM
authors.lastname: Hart
authors.affiliation: Program in Tissue Immunity and Repair, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: Rafael
authors.initials: R
authors.lastname: de Queiroz Prado
authors.affiliation: Program in Tissue Immunity and Repair, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: Joshua
authors.initials: J
authors.lastname: Sciurba
authors.affiliation: Program in Tissue Immunity and Repair, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: Luke
authors.initials: L
authors.lastname: Barron
authors.affiliation: Program in Tissue Immunity and Repair, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.|Tissue Fibrosis and Repair Group, Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, UK.
authors.forename: Lee A
authors.initials: LA
authors.lastname: Borthwick
authors.affiliation: United States Department of Agriculture, Agricultural Research Service, Beltsville Human Nutrition Center, Beltsville, Maryland, USA.
authors.forename: Allen D
authors.initials: AD
authors.lastname: Smith
authors.affiliation: Program in Tissue Immunity and Repair, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: Margaret
authors.initials: M
authors.lastname: Mentink-Kane
authors.affiliation: Program in Tissue Immunity and Repair, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: Sandra
authors.initials: S
authors.lastname: White
authors.affiliation: Program in Tissue Immunity and Repair, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: Robert W
authors.initials: RW
authors.lastname: Thompson
authors.affiliation: Program in Tissue Immunity and Repair, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: Allen W
authors.initials: AW
authors.lastname: Cheever
authors.affiliation: Infectious Disease Pathology Section, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, Maryland, USA.
authors.forename: Kevin
authors.initials: K
authors.lastname: Bock
authors.affiliation: Infectious Disease Pathology Section, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, Maryland, USA.
authors.forename: Ian
authors.initials: I
authors.lastname: Moore
authors.affiliation: Inflammation and Immunity, Pfizer Worldwide R&D, Cambridge, Massachusetts, USA.
authors.forename: Lori J
authors.initials: LJ
authors.lastname: Fitz
authors.affiliation: United States Department of Agriculture, Agricultural Research Service, Beltsville Human Nutrition Center, Beltsville, Maryland, USA.
authors.forename: Joseph F
authors.initials: JF
authors.lastname: Urban
authors.affiliation: Program in Tissue Immunity and Repair, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Wynn
mesh_terms: D000818:Animals; D002688:Chitinases / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D018118:Chloride Channels / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D005434:Flow Cytometry; D041981:Gastrointestinal Tract / Q000276:immunology* / Q000378:metabolism / Q000469:parasitology; D015870:Gene Expression / Q000276:immunology; D006729:Hormones, Ectopic / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D006790:Host-Parasite Interactions / Q000276:immunology; D006967:Hypersensitivity / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D007109:Immunity / Q000235:genetics / Q000276:immunology*; D036341:Intercellular Signaling Peptides and Proteins; D018793:Interleukin-13 / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D037102:Lectins / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D008168:Lung / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008856:Microscopy, Fluorescence; D009351:Nematospiroides dubius / Q000276:immunology / Q000502:physiology; D009559:Nippostrongylus / Q000276:immunology / Q000502:physiology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017206:Strongylida Infections / Q000276:immunology* / Q000378:metabolism / Q000469:parasitology; D001619:beta-N-Acetylhexosaminidases / Q000235:genetics / Q000276:immunology / Q000378:metabolism
chemical_list: D018118:Chloride Channels; C116464:Clca3a1 protein, mouse; D006729:Hormones, Ectopic; D036341:Intercellular Signaling Peptides and Proteins; D018793:Interleukin-13; D037102:Lectins; C486522:Retnlb protein, mouse; C499255:AMCase, mouse; D002688:Chitinases; C429541:Chil3 protein, mouse; D001619:beta-N-Acetylhexosaminidases