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

Eri Ishikawa, Tetsuaki Ishikawa, Yasu S. Morita, Kenji Toyonaga, Hisakata Yamada, Osamu Takeuchi, Taroh Kinoshita, Shizuo Akira, Yasunobu Yoshikai, Shou Yamasaki

    Research output: Contribution to journalArticle

    399 Citations (Scopus)

    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.

    Original languageEnglish
    Pages (from-to)2879-2888
    Number of pages10
    JournalJournal of Experimental Medicine
    Volume206
    Issue number13
    DOIs
    Publication statusPublished - Dec 21 2009

    Fingerprint

    Cord Factors
    C-Type Lectins
    Glycolipids
    Macrophages
    Mycobacterium
    Granuloma
    Mycobacterium tuberculosis
    Cytokines
    Trehalose
    Cell Wall

    All Science Journal Classification (ASJC) codes

    • Immunology and Allergy
    • Immunology

    Cite this

    Ishikawa, E., Ishikawa, T., Morita, Y. S., Toyonaga, K., Yamada, H., Takeuchi, O., ... Yamasaki, S. (2009). Direct recognition of the mycobacterial glycolipid, trehalose dimycolate, by C-type lectin Mincle. Journal of Experimental Medicine, 206(13), 2879-2888. https://doi.org/10.1084/jem.20091750

    Direct recognition of the mycobacterial glycolipid, trehalose dimycolate, by C-type lectin Mincle. / Ishikawa, Eri; Ishikawa, Tetsuaki; Morita, Yasu S.; Toyonaga, Kenji; Yamada, Hisakata; Takeuchi, Osamu; Kinoshita, Taroh; Akira, Shizuo; Yoshikai, Yasunobu; Yamasaki, Shou.

    In: Journal of Experimental Medicine, Vol. 206, No. 13, 21.12.2009, p. 2879-2888.

    Research output: Contribution to journalArticle

    Ishikawa, E, Ishikawa, T, Morita, YS, Toyonaga, K, Yamada, H, Takeuchi, O, Kinoshita, T, Akira, S, Yoshikai, Y & Yamasaki, S 2009, 'Direct recognition of the mycobacterial glycolipid, trehalose dimycolate, by C-type lectin Mincle', Journal of Experimental Medicine, vol. 206, no. 13, pp. 2879-2888. https://doi.org/10.1084/jem.20091750
    Ishikawa E, Ishikawa T, Morita YS, Toyonaga K, Yamada H, Takeuchi O et al. Direct recognition of the mycobacterial glycolipid, trehalose dimycolate, by C-type lectin Mincle. Journal of Experimental Medicine. 2009 Dec 21;206(13):2879-2888. https://doi.org/10.1084/jem.20091750
    Ishikawa, Eri ; Ishikawa, Tetsuaki ; Morita, Yasu S. ; Toyonaga, Kenji ; Yamada, Hisakata ; Takeuchi, Osamu ; Kinoshita, Taroh ; Akira, Shizuo ; Yoshikai, Yasunobu ; Yamasaki, Shou. / Direct recognition of the mycobacterial glycolipid, trehalose dimycolate, by C-type lectin Mincle. In: Journal of Experimental Medicine. 2009 ; Vol. 206, No. 13. pp. 2879-2888.
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