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

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

Author information

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.

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.

PMID:
25176311
DOI:
10.1016/j.immuni.2014.08.005
[Indexed for MEDLINE]
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