Dectin-2 is a direct receptor for mannose-capped lipoarabinomannan of mycobacteria

Akiko Yonekawa; Shinobu Saijo; Yoshihiko Hoshino; Yasunobu Miyake; Eri Ishikawa; Maho Suzukawa; Hiromasa Inoue; Masato Tanaka; Mitsutoshi Yoneyama; Masatsugu Oh-Hora; Koichi Akashi; Sho Yamasaki

doi:10.1016/j.immuni.2014.08.005

Dectin-2 is a direct receptor for mannose-capped lipoarabinomannan of mycobacteria

Immunity. 2014 Sep 18;41(3):402-413. doi: 10.1016/j.immuni.2014.08.005. Epub 2014 Aug 28.

Authors

Affiliations

¹ 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.
² 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.
³ Leprosy Research Center, National Institute of Infectious Diseases, Tokyo 189-0002, Japan.
⁴ Division of Molecular Immunology, Medical Institute of Bioregulation, Kyushu University, Fukuoka 812-8582, Japan.
⁵ Center for Pulmonary Diseases, National Hospital Organization, Tokyo National Hospital, Tokyo 204-8585, Japan.
⁶ Department of Pulmonary Medicine, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima 890-8544, Japan.
⁷ Laboratory for Immune Regulation, School of Life Sciences, Tokyo University of Pharmacy and Life Sciences, Tokyo 192-0392, Japan.
⁸ Division of Molecular Immunology, Medical Mycology Research Center, Chiba University, Chiba 260-8673, Japan.
⁹ 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.
¹⁰ Department of Medicine and Biosystemic Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan.
¹¹ 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.

PMID: 25176311
DOI: 10.1016/j.immuni.2014.08.005

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Antigens, CD / genetics
Cell Adhesion Molecules / genetics
Cytokines / biosynthesis
Dendritic Cells / immunology
Encephalomyelitis, Autoimmune, Experimental / genetics
Encephalomyelitis, Autoimmune, Experimental / immunology*
Inflammation / immunology
Interferon-gamma / biosynthesis
Interleukin-10 / biosynthesis
Lectins, C-Type / genetics
Lectins, C-Type / immunology*
Lipopolysaccharides / chemistry
Lipopolysaccharides / immunology*
Mannose / chemistry
Mannose Receptor
Mannose-Binding Lectins / immunology
Mice
Mice, Knockout
Mycobacterium Infections / genetics
Mycobacterium Infections / immunology*
Mycobacterium bovis / immunology
Mycobacterium tuberculosis / immunology
Myeloid Differentiation Factor 88 / genetics
Protein Binding / immunology
Receptors, Cell Surface / genetics
Receptors, Cell Surface / immunology
Receptors, Immunologic / genetics
T-Lymphocytes / immunology

Substances

Antigens, CD
Cell Adhesion Molecules
Clec4d protein, mouse
Cytokines
DC-specific ICAM-3 grabbing nonintegrin
IL10 protein, mouse
Lectins, C-Type
Lipopolysaccharides
Mannose Receptor
Mannose-Binding Lectins
Myd88 protein, mouse
Myeloid Differentiation Factor 88
Receptors, Cell Surface
Receptors, Immunologic
SIGNR3 protein, mouse
dectin-2, mouse
lipoarabinomannan
Interleukin-10
Interferon-gamma
Mannose