Mincle: 20 years of a versatile sensor of insults

Macrophage-inducible C-type lectin, better known as Mincle, is a member of the C-type lectin receptor family and is encoded by Clec4e. Mincle was an orphan receptor for a long time after having been discovered as a lipopolysaccharide-induced protein, yet later an adjuvant glycolipid in mycobacteria-trehalose dimycolate-was identified as a ligand. Ligands for Mincle were also found existing in bacteria, fungi and even mammals. When confronted with foreign elements, Mincle can recognize characteristic pathogen-associated molecular patterns, mostly glycolipids, from Mycobacterium tuberculosis and other pathogens, and thus induce immune responses against infection. To maintain self-homeostasis, Mincle can recognize lipid-based damage-associated molecular patterns, thereby monitoring the internal environment. The mechanism by which Mincle functions in the immune system is also becoming more clear along with the identification of its ligands. Being expressed widely on antigen-presenting cells, Mincle activation leads to the production of cytokines and chemokines, neutrophil infiltration and other inflammatory responses. Besides, Mincle can induce acquired immunity such as antigen-specific T-cell responses and antibody production as an adjuvant receptor. In this review, we will retrospectively sketch the discovery and study of Mincle, and outline some current work on this receptor.