Ishikawa, E. et al. Direct recognition of the mycobacterial glycolipid, trehalose dimycolate, by C-type lectin Mincle. J. Exp. Med. 206, 2879-2888

Division of Molecular Immunology, Medical Institute of Bioregulation, Kyushu University, Fukuoka 812-8582, Japan.
Journal of Experimental Medicine (Impact Factor: 12.52). 12/2009; 206(13):2879-88. DOI: 10.1084/jem.20091750
Source: PubMed


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.

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    • "Dectin-1 was found to play a role in dendritic cell IL-12 production in response to mycobacteria in vitro; however , loss of this receptor did not alter susceptibility to infection in vivo (Marakalala et al., 2011). Mincle recognizes trehalose- 6,6 0 -dimycolate (TDM or cord factor) and was found to mediate robust responses to this mycobacterial cell wall glycolipid both in vitro and in vivo (Ishikawa et al., 2009; Schoenen et al., 2010). However, the role of Mincle in vivo is controversial, with some studies describing no clear role for this receptor during mycobacterial infection (Behler et al., 2012; Heitmann et al., 2013). "
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