TREM2 is a Receptor for Non-glycosylated Mycolic Acids of Mycobacteria That Limits Anti-mycobacterial Macrophage Activation

Overview

Journal Nat Commun

Specialty Biology

Date 2021 Apr 17

PMID 33863908

Citations 26

Authors

Eiichi Iizasa

Yasushi Chuma

Takayuki Uematsu

Mio Kubota

Hiroaki Kawaguchi

Masayuki Umemura

Kenji Toyonaga

Hideyasu Kiyohara

Ikuya Yano

Marco Colonna

Masahiko Sugita

Goro Matsuzaki

Sho Yamasaki

Hiroki Yoshida

Hiromitsu Hara

Affiliations

Soon will be listed here.

Abstract

Mycobacterial cell-wall glycolipids elicit an anti-mycobacterial immune response via FcRγ-associated C-type lectin receptors, including Mincle, and caspase-recruitment domain family member 9 (CARD9). Additionally, mycobacteria harbor immuno-evasive cell-wall lipids associated with virulence and latency; however, a mechanism of action is unclear. Here, we show that the DAP12-associated triggering receptor expressed on myeloid cells 2 (TREM2) recognizes mycobacterial cell-wall mycolic acid (MA)-containing lipids and suggest a mechanism by which mycobacteria control host immunity via TREM2. Macrophages respond to glycosylated MA-containing lipids in a Mincle/FcRγ/CARD9-dependent manner to produce inflammatory cytokines and recruit inducible nitric oxide synthase (iNOS)-positive mycobactericidal macrophages. Conversely, macrophages respond to non-glycosylated MAs in a TREM2/DAP12-dependent but CARD9-independent manner to recruit iNOS-negative mycobacterium-permissive macrophages. Furthermore, TREM2 deletion enhances Mincle-induced macrophage activation in vitro and inflammation in vivo and accelerates the elimination of mycobacterial infection, suggesting that TREM2-DAP12 signaling counteracts Mincle-FcRγ-CARD9-mediated anti-mycobacterial immunity. Mycobacteria, therefore, harness TREM2 for immune evasion.

Citing Articles

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