Chemistry and Biology of Mycobacterial Glycolipids

Mycobacterial glycolipid trehalose-6,6'-dimycolate (TDM) has been extensively studied due to its various biological activities, including toxicity in mice, adjuvant activity, antitumor activity, and anti-infective activity. In addition to natural TDM, various TDM analogues have been synthesized to examine the structure-activity relationship of TDM. The receptor that recognizes TDM remained unknown for many years, until the receptor was identified as macrophage-inducible C-type lectin (Mincle), a C-type lectin receptor expressed on macrophages. Recently, Mincle has been reported to recognize other glycolipids, including cholesterol acyl α-glucoside, a metabolic product of Helicobacter pylori, as well as mycobacterial glycolipids. In addition, Mincle recognizes not only exogenous (glyco)lipids but also various (glyco)lipids released from a damaged cell itself as endogenous ligands, such as β-glucosylceramide, and induces immune responses, such as inflammation.