title: Dectin-2 deficiency promotes Th2 response and mucin production in the lungs after pulmonary infection with Cryptococcus neoformans.
abstract: Dectin-2 is a C-type lectin receptor that recognizes high mannose polysaccharides. Cryptococcus neoformans, a yeast-form fungal pathogen, is rich in polysaccharides in its cell wall and capsule. In the present study, we analyzed the role of Dectin-2 in the host defense against C. neoformans infection. In Dectin-2 gene-disrupted (knockout) (Dectin-2KO) mice, the clearance of this fungus and the inflammatory response, as shown by histological analysis and accumulation of leukocytes in infected lungs, were comparable to those in wild-type (WT) mice. The production of type 2 helper T (Th2) cytokines in lungs was higher in Dectin-2KO mice than in WT mice after infection, whereas there was no difference in the levels of production of Th1, Th17, and proinflammatory cytokines between these mice. Mucin production was significantly increased in Dectin-2KO mice, and this increase was reversed by administration of anti-interleukin 4 (IL-4) monoclonal antibody (MAb). The levels of expression of β1-defensin, cathelicidin, surfactant protein A (Sp-A), and Sp-D in infected lungs were comparable between these mice. In in vitro experiments, IL-12p40 and tumor necrosis factor alpha (TNF-α) production and expression of CD86 and major histocompatibility complex (MHC) class II by bone marrow-derived dendritic cells and alveolar macrophages were completely abrogated in Dectin-2KO mice. Finally, the disrupted lysates of C. neoformans, but not of whole yeast cells, activated Dectin-2-triggered signaling in an assay with nuclear factor of activated T cells (NFAT)-green fluorescent protein (GFP) reporter cells expressing this receptor. These results suggest that Dectin-2 may oppose the Th2 response and IL-4-dependent mucin production in the lungs after infection with C. neoformans, and it may not be required for the production of Th1, Th17, and proinflammatory cytokines or for clearance of this fungal pathogen.
authors.affiliation: Department of Medical Microbiology, Mycology and Immunology, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan.
authors.forename: Yuri
authors.initials: Y
authors.lastname: Nakamura
authors.affiliation: Department of Medical Microbiology, Mycology and Immunology, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan.
authors.forename: Ko
authors.initials: K
authors.lastname: Sato
authors.affiliation: Department of Medical Microbiology, Mycology and Immunology, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan.
authors.forename: Hideki
authors.initials: H
authors.lastname: Yamamoto
authors.affiliation: Department of Plastic and Reconstructive Surgery, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan.
authors.forename: Kana
authors.initials: K
authors.lastname: Matsumura
authors.affiliation: Department of Medical Microbiology, Mycology and Immunology, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan.
authors.forename: Ikumi
authors.initials: I
authors.lastname: Matsumoto
authors.affiliation: Department of Medical Microbiology, Mycology and Immunology, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan.
authors.forename: Toshiki
authors.initials: T
authors.lastname: Nomura
authors.affiliation: Department of Medical Microbiology, Mycology and Immunology, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan.
authors.forename: Tomomitsu
authors.initials: T
authors.lastname: Miyasaka
authors.affiliation: Department of Medical Microbiology, Mycology and Immunology, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan.
authors.forename: Keiko
authors.initials: K
authors.lastname: Ishii
authors.affiliation: Department of Science of Nursing Practice, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan.
authors.forename: Emi
authors.initials: E
authors.lastname: Kanno
authors.affiliation: Department of Plastic and Reconstructive Surgery, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Tachi
authors.affiliation: Division of Molecular Immunology, Medical Institute of Bioregulation, Kyushu University, Fukuoka, Japan.
authors.forename: Sho
authors.initials: S
authors.lastname: Yamasaki
authors.affiliation: Division of Molecular Immunology, Medical Mycology Research Center, Chiba University, Chiba, Japan.
authors.forename: Shinobu
authors.initials: S
authors.lastname: Saijo
authors.affiliation: Center for Animal Disease Models, Research Institute for Biological Sciences, Tokyo University of Science, Noda, Chiba, Japan.
authors.forename: Yoichiro
authors.initials: Y
authors.lastname: Iwakura
authors.affiliation: Department of Medical Microbiology, Mycology and Immunology, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan kawakami@med.tohoku.ac.jp.
authors.forename: Kazuyoshi
authors.initials: K
authors.lastname: Kawakami
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D023181:Antimicrobial Cationic Peptides / Q000096:biosynthesis; D051940:B7-2 Antigen / Q000096:biosynthesis; D002478:Cells, Cultured; D003453:Cryptococcosis / Q000276:immunology*; D003455:Cryptococcus neoformans / Q000276:immunology*; D023082:Defensins / Q000096:biosynthesis; D003713:Dendritic Cells / Q000276:immunology; D005260:Female; D049452:Green Fluorescent Proteins / Q000235:genetics; D000949:Histocompatibility Antigens Class II / Q000096:biosynthesis; D007249:Inflammation / Q000235:genetics / Q000276:immunology; D053762:Interleukin-12 Subunit p40 / Q000096:biosynthesis; D015847:Interleukin-4 / Q000276:immunology; D037181:Lectins, C-Type / Q000235:genetics* / Q000276:immunology; D008168:Lung / Q000382:microbiology / Q000473:pathology; D008172:Lung Diseases, Fungal / Q000276:immunology; D016676:Macrophages, Alveolar / Q000276:immunology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009077:Mucins / Q000096:biosynthesis; D037662:Pulmonary Surfactant-Associated Protein A / Q000096:biosynthesis; D037663:Pulmonary Surfactant-Associated Protein D / Q000096:biosynthesis; D018417:Th1 Cells / Q000276:immunology; D058504:Th17 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis; D054804:Cathelicidins
chemical_list: D000911:Antibodies, Monoclonal; D023181:Antimicrobial Cationic Peptides; D051940:B7-2 Antigen; C497965:Cd86 protein, mouse; D023082:Defensins; D000949:Histocompatibility Antigens Class II; D053762:Interleukin-12 Subunit p40; D037181:Lectins, C-Type; D009077:Mucins; D037662:Pulmonary Surfactant-Associated Protein A; D037663:Pulmonary Surfactant-Associated Protein D; D014409:Tumor Necrosis Factor-alpha; C445340:dectin-2, mouse; D049452:Green Fluorescent Proteins; D015847:Interleukin-4; D054804:Cathelicidins