Glycerol Monomycolate Is a Novel Ligand for the Human, but Not Mouse Macrophage Inducible C-type Lectin, Mincle

• DOI: 10.1074/jbc.m114.566489
• Publication Date: 2014-04-15T00:14:14Z
• Authors: Yuki Hattori; Daisuke Morita; Nagatoshi Fujiwara; Daiki Mori; Takashi Nakamura; Hideyoshi Harashima; Sho Yamasaki; Masahiko Sugita
• Keywords: Ectodomain; C-type lectin

An array of lipidic compounds that constitute the cell wall mycobacteria is recognized by host receptors. Examples include trehalose dimycolate (TDM), which a major surface-exposed glycolipid mycobacteria, interacts with macrophage inducible C-type lectin, Mincle, and exerts its highly potent adjuvant functions. Recent evidence has suggested glycerol monomycolate (GroMM), another mycolate-containing lipid species produced can stimulate innate immune cells; however, specific receptors have yet to be identified. We here demonstrated transfectants expressing human Mincle (hMincle) reacted both TDM GroMM, while those mouse (mMincle) only failed recognize GroMM. Studies using domain swap chimeras confirmed ectodomain hMincle, but not mMincle, interacted site-directed mutagenesis analyses revealed short stretches amino acid residues at positions 174–176 195–196 were involved in GroMM recognition. To further substantiate differential recognition hMincle transgenic/mMincle knock-out mice (i.e. hMincle+ mice) established compared non-transgenic mMincle+ mice). showed macrophages derived from activated inflammatory cytokines, whereas did exhibit any reactivity Furthermore, local responses elicited GroMM-injected skin hMincle+, mice. These results unique ligand for mMincle.