Cutting Edge: Mincle Is Essential for Recognition and Adjuvanticity of the Mycobacterial Cord Factor and its Synthetic Analog Trehalose-Dibehenate

Abstract

Material Supplementary 3.DC1http://www.jimmunol.org/content/suppl/2010/02/15/jimmunol.090401

Receptor Mincle promotes skin allergies and is capable of recognizing cholesterol sulfate

“…Therefore, endogenous Mincle ligands may serve as auto-adjuvants, activating the innate immune system. Interestingly, the activation of Mincle by its ligands, such as trehalose-6,6′-dimycolate from M. tuberculosis or the synthetic adjuvant trehalose dibehenate, promotes Th1/Th17 T-cell responses (9,13,37). We found in allergic inflamed ears from Mincle-KO mice a suppressed production of IL-17A, which is regarded as a signature cytokine for Th17 cells (38).…”

“…The ligation of Mincle by its ligands leads to the interaction of Mincle with the adaptor protein Fc receptor γ-chain (FcRγ) and the recruitment of spleen tyrosine kinase (Syk) (7,8). The signal is subsequently transmitted to NF-κB via the CARD9-BCL10-MALT1 pathway, leading to the production of a spectrum of proinflammatory cytokines (6,8,9).…”

Macrophage-inducible C-type lectin underlies obesity-induced adipose tissue fibrosis

“…Macrophage-inducible C-type lectin (Mincle, Clec4e or Clecsf9) is a pathogen sensor that recognizes pathogenic fungi and Mycobacterium tuberculosis [13][14][15][16] , and as the name implies, it is induced in macrophages by lipopolysaccharide through Toll-like receptor 4 (TLR4; ref. 17).…”

Broadening Our View About the Role of Mycobacterium tuberculosis Cell Envelope Components During Infection: A Battle for Survival

“…Inhibition of the phagosome maturation is observed after phagocytosis of virulent strains of M.tb, allowing the bacillus to survive within the phagocyte (Schlesinger LS et al, 2008). Recently, Mincle (macrophage-inducible C-type lectin) (Yamasaki et al, 2008) on the macrophage surface, has been shown to recognize M.tb TDM, and working together with the Fcreceptor transmembrane segment induces pro-inflammation (Ishikawa et al, 2009;Schoenen et al, 2010). In the case of M.tb TMM, this is shown to be used by the bacillus to transfer mycolic acids towards molecules like the wall-linked AG.…”

“…Dectin-1 (dendritic cell-associated C-type lectin 1), a -glucan receptor, in combination with TLR2 has also been shown involved in the immune response against M.tb (Yadav & Schorey, 2006). Recently, Mincle (macrophageinducible C-type lectin) (Yamasaki et al, 2008) on the macrophage surface, has been shown to specifically recognize M.tb TDM, inducing a pro-inflammatory response by working together with the Fc receptor transmembrane segment (Ishikawa et al, 2009;Schoenen et al, 2010) (Table 1). Conversely, Fc receptors do not play a role in the phagocytosis of M.tb in the absence of specific antibody (Schlesinger et al, 1990).…”