Direct recognition of the mycobacterial glycolipid, trehalose dimycolate, by C-type lectin Mincle

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Direct recognition of the mycobacterial glycolipid, trehalose dimycolate, by C-type lectin Mincle

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Kyushu Univ. Production Kyushu Univ. Production
Responsibility:
Ishikawa, Eri(Division of Molecular Immunology, Medical Institute of Bioregulation, Kyushu University)
石川, 絵里(九州大学生体防御医学研究所)
Ishikawa, Tetsuaki(Division of Molecular Immunology, Medical Institute of Bioregulation, Kyushu University | Cell Signaling, Chiba University School of Medicine)

石川, 哲章(九州大学生体防御医学研究所 | 千葉大学医学部)
Morita, Yasu S.(Department of Immunoregulation, WPI Immunology Frontier Research Center, Osaka University | Laboratory of Immunoglycobiology, WPI Immunology Frontier Research Center, Osaka University)
森田, 康裕(大阪大学免疫学フロンティア研究センター)
Toyonaga, Kenji(Division of Molecular Immunology, Medical Institute of Bioregulation, Kyushu University)
豊永, 憲司(九州大学生体防御医学研究所)
Yamada, Hisakata(Division of Host Defense, Medical Institute of Bioregulation, Kyushu University)
山田, 久方(九州大学生体防御医学研究所)
Takeuchi, Osamu(Department of Host Defense, Research Institute for Microbial Diseases, WPI Immunology Frontier Research Center, Osaka University | Laboratory of Host Defense, WPI Immunology Frontier Research Center, Osaka University)
竹内, 理(大阪大学免疫学フロンティア研究センター)
Kinoshita, Taroh(Department of Immunoregulation, WPI Immunology Frontier Research Center, Osaka University | Laboratory of Immunoglycobiology, WPI Immunology Frontier Research Center, Osaka University)
木下, タロウ(大阪大学免疫学フロンティア研究センター)
Akira, Shizuo(Department of Host Defense, Research Institute for Microbial Diseases, WPI Immunology Frontier Research Center, Osaka University | Laboratory of Host Defense, WPI Immunology Frontier Research Center, Osaka University)
審良, 静男(大阪大学免疫学フロンティア研究センター)
Yoshikai, Yasunobu(Division of Host Defense, Medical Institute of Bioregulation, Kyushu University)
吉開, 泰信(九州大学生体防御医学研究所)
Yamasaki, Sho(Division of Molecular Immunology, Medical Institute of Bioregulation, Kyushu University)
山崎, 晶(九州大学生体防御医学研究所)

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Language:
English
Publication info:
Journal of Experimental Medicine. 206, (13), pp. 2879-2888-, 2009-12-14. Rockefeller University Press
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Publisher
Abstract:
Tuberculosis remains a fatal disease caused by Mycobacterium tuberculosis, which contains various unique components that affect the host immune system. Trehalose-6,6'-dimycolate (TDM; also called cord factor) is a mycobacterial cell wall glycolipid that is the most studied immunostimulatory component of M. tuberculosis. Despite five decades of research on TDM, its host receptor has not been clearly identified. Here, we demonstrate that macrophage inducible C-type lectin (Mincle) is an essential receptor for TDM. Heat-killed mycobacteria activated Mincle-expressing cells, but the activity was lost upon delipidation of the bacteria; analysis of the lipid extracts identified TDM as a Mincle ligand. TDM activated macrophages to produce inflammatory cytokines and nitric oxide, which are completely suppressed in Mincle-deficient macrophages. In vivo TDM administration induced a robust elevation of inflammatory cytokines in sera and characteristic lung inflammation, such as granuloma formation. However, no TDM-induced lung granuloma was formed in Mincle-deficient mice. Whole mycobacteria were able to activate macrophages even in MyD88-deficient background, but the activation was significantly diminished in Mincle/MyD88 double-deficient macrophages. These results demonstrate that Mincle is an essential receptor for the mycobacterial glycolipid, TDM. Read more
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