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TREM2 is a receptor for non-glycosylated mycolic acids of mycobacteria that limits anti-mycobacterial macrophage activation

発表形態:
原著論文
主要業績:
主要業績
単著・共著:
共著
発表年月:
2021年04月
DOI:
10.1038/s41467-021-22620-3
会議属性:
指定なし
査読:
有り
リンク情報:

日本語フィールド

著者:
*Ei'ichi 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
題名:
TREM2 is a receptor for non-glycosylated mycolic acids of mycobacteria that limits anti-mycobacterial macrophage activation
発表情報:
Nat Commun 巻: 12 号: 1 ページ: 2299
キーワード:
概要:
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.
抄録:

英語フィールド

Author:
*Ei'ichi 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
Title:
TREM2 is a receptor for non-glycosylated mycolic acids of mycobacteria that limits anti-mycobacterial macrophage activation
Announcement information:
Nat Commun Vol: 12 Issue: 1 Page: 2299
An 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.


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