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Title :TREM2 is a receptor for non-glycosylated mycolic acids of mycobacteria that limits antimycobacterial macrophage activation
Authors :Iizasa, Ei'ichi
Chuma, Yasushi
Uematsu, Takayuki
Kubota, Mio
Kawaguchi, Hiroaki
Umemura, Masayuki
Toyonaga, Kenji
Kiyohara, Hideyasu
Yano, Ikuya
Colonna, Marco
Sugita, Masahiko
Matsuzaki, Goro
Yamasaki, Sho
Yoshida, Hiroki
Hara, Hiromitsu
Issue Date :16-Apr-2021
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. Download PDF
URL :https://doi.org/10.1038/s41467-021-22620-3
Type Local :雑誌掲載論文
ISSN :2041-1723
Publisher :Springer Nature
URI :http://hdl.handle.net/20.500.12000/50025
Citation :Nature Communications Vol.12
Appears in Collections:Peer-reviewed Journal Articles(Tropical Biosphere Research Center)

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