title: Dectin-2 is a direct receptor for mannose-capped lipoarabinomannan of mycobacteria.
abstract: Mycobacteria possess various immunomodulatory molecules on the cell wall. Mannose-capped lipoarabinomannan (Man-LAM), a major lipoglycan of Mycobacterium tuberculosis, has long been known to have both inhibitory and stimulatory effects on host immunity. However, the direct Man-LAM receptor that explains its pleiotropic activities has not been clearly identified. Here, we report that a C-type lectin receptor Dectin-2 (gene symbol Clec4n) is a direct receptor for Man-LAM. Man-LAM activated bone-marrow-derived dendritic cells (BMDCs) to produce pro- and anti-inflammatory cytokines, whereas it was completely abrogated in Clec4n(-/-) BMDCs. Man-LAM promoted antigen-specific T cell responses through Dectin-2 on DCs. Furthermore, Man-LAM induced experimental autoimmune encephalitis (EAE) as an adjuvant in mice, whereas Clec4n(-/-) mice were resistant. Upon mycobacterial infection, Clec4n(-/-) mice showed augmented lung pathology. These results demonstrate that Dectin-2 contributes to host immunity against mycobacterial infection through the recognition of Man-LAM.
authors.affiliation: Division of Molecular Immunology, Medical Institute of Bioregulation, Kyushu University, Fukuoka 812-8582, Japan; Department of Medicine and Biosystemic Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan.
authors.forename: Akiko
authors.initials: A
authors.lastname: Yonekawa
authors.affiliation: Division of Molecular Immunology, Medical Mycology Research Center, Chiba University, Chiba 260-8673, Japan; PRESTO, Japan Science and Technology Agency (JST), Saitama 332-0012, Japan.
authors.forename: Shinobu
authors.initials: S
authors.lastname: Saijo
authors.affiliation: Leprosy Research Center, National Institute of Infectious Diseases, Tokyo 189-0002, Japan.
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Hoshino
authors.affiliation: Division of Molecular Immunology, Medical Institute of Bioregulation, Kyushu University, Fukuoka 812-8582, Japan.
authors.forename: Yasunobu
authors.initials: Y
authors.lastname: Miyake
authors.affiliation: Division of Molecular Immunology, Medical Institute of Bioregulation, Kyushu University, Fukuoka 812-8582, Japan.
authors.forename: Eri
authors.initials: E
authors.lastname: Ishikawa
authors.affiliation: Center for Pulmonary Diseases, National Hospital Organization, Tokyo National Hospital, Tokyo 204-8585, Japan.
authors.forename: Maho
authors.initials: M
authors.lastname: Suzukawa
authors.affiliation: Department of Pulmonary Medicine, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima 890-8544, Japan.
authors.forename: Hiromasa
authors.initials: H
authors.lastname: Inoue
authors.affiliation: Laboratory for Immune Regulation, School of Life Sciences, Tokyo University of Pharmacy and Life Sciences, Tokyo 192-0392, Japan.
authors.forename: Masato
authors.initials: M
authors.lastname: Tanaka
authors.affiliation: Division of Molecular Immunology, Medical Mycology Research Center, Chiba University, Chiba 260-8673, Japan.
authors.forename: Mitsutoshi
authors.initials: M
authors.lastname: Yoneyama
authors.affiliation: Division of Molecular Immunology, Medical Institute of Bioregulation, Kyushu University, Fukuoka 812-8582, Japan; PRESTO, Japan Science and Technology Agency (JST), Saitama 332-0012, Japan.
authors.forename: Masatsugu
authors.initials: M
authors.lastname: Oh-Hora
authors.affiliation: Department of Medicine and Biosystemic Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan.
authors.forename: Koichi
authors.initials: K
authors.lastname: Akashi
authors.affiliation: Division of Molecular Immunology, Medical Institute of Bioregulation, Kyushu University, Fukuoka 812-8582, Japan; Division of Molecular Immunology, Medical Mycology Research Center, Chiba University, Chiba 260-8673, Japan. Electronic address: yamasaki@bioreg.kyushu-u.ac.jp.
authors.forename: Sho
authors.initials: S
authors.lastname: Yamasaki
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000235:genetics; D015815:Cell Adhesion Molecules / Q000235:genetics; D016207:Cytokines / Q000096:biosynthesis; D003713:Dendritic Cells / Q000276:immunology; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000235:genetics / Q000276:immunology*; D007249:Inflammation / Q000276:immunology; D007371:Interferon-gamma / Q000096:biosynthesis; D016753:Interleukin-10 / Q000096:biosynthesis; D037181:Lectins, C-Type / Q000235:genetics / Q000276:immunology*; D008070:Lipopolysaccharides / Q000737:chemistry / Q000276:immunology*; D008358:Mannose / Q000737:chemistry; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins / Q000276:immunology; D051379:Mice; D018345:Mice, Knockout; D009164:Mycobacterium Infections / Q000235:genetics / Q000276:immunology*; D009163:Mycobacterium bovis / Q000276:immunology; D009169:Mycobacterium tuberculosis / Q000276:immunology; D053594:Myeloid Differentiation Factor 88 / Q000235:genetics; D011485:Protein Binding / Q000276:immunology; D011956:Receptors, Cell Surface / Q000235:genetics / Q000276:immunology; D011971:Receptors, Immunologic / Q000235:genetics; D013601:T-Lymphocytes / Q000276:immunology; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin
chemical_list: D015703:Antigens, CD; D015815:Cell Adhesion Molecules; D016207:Cytokines; D007371:Interferon-gamma; D016753:Interleukin-10; D037181:Lectins, C-Type; D008070:Lipopolysaccharides; D008358:Mannose; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins; D053594:Myeloid Differentiation Factor 88; D011956:Receptors, Cell Surface; D011971:Receptors, Immunologic; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin; C584161:Clec4d protein, mouse; C556062:IL10 protein, mouse; C507780:Myd88 protein, mouse; C494354:SIGNR3 protein, mouse; C445340:dectin-2, mouse; C050016:lipoarabinomannan