TREM2 is a receptor for non-glycosylated mycolic acids of mycobacteria that limits anti-mycobacterial macrophage activation.
TREM2 is a receptor for non-glycosylated mycolic acids of mycobacteria that limits anti-mycobacterial macrophage activation.
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TREM2是分枝杆菌的非糖基化分枝菌酸的受体，其限制抗分枝杆菌巨噬细胞活化。
DOI：
10.1038/s41467-021-22620-3
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发表时间：
2021-04-16
影响因子：
16.6
通讯作者：
Hara H
中科院分区：
文献类型：
--
作者：
Iizasa E;Chuma Y;Uematsu T;Kubota M;Kawaguchi H;Umemura M;Toyonaga K;Kiyohara H;Yano I;Colonna M;Sugita M;Matsuzaki G;Yamasaki S;Yoshida H;Hara H
分枝杆菌细胞壁糖脂通过γ相关的C型凝集素受体，包括Mincle和Caspase招募结构域家族成员9(CARD9)诱导抗分枝杆菌免疫反应。此外，分枝杆菌含有与毒力和潜伏期相关的免疫逃逸细胞壁脂；然而，作用机制尚不清楚。在这里，我们证明了表达在髓样细胞2上的DAP12相关触发受体(TREM2)识别含有分枝杆菌细胞壁分枝杆菌酸(MA)的脂类，并提出了分枝杆菌通过TREM2控制宿主免疫的机制。巨噬细胞以Mincle/Fcr、γ/CARD9依赖的方式对糖基化的MA脂类作出反应，产生炎性细胞因子并招募诱导型一氧化氮合酶(INOS)阳性的杀分枝杆菌巨噬细胞。相反，巨噬细胞以依赖于TREM2/DAP12但不依赖于CARD9的方式对非糖基化的MA作出反应，以招募iNOS阴性的分枝杆菌允许的巨噬细胞。此外，TREM2缺失增强了Mincle诱导的巨噬细胞在体外的活化和体内的炎症反应，并加速了分枝杆菌感染的消除，提示TREM2-DAP12信号通路抵消了Mincle-FCRγ-CARD9介导的抗分枝杆菌免疫。因此，分枝杆菌利用TREM2来逃避免疫。分枝杆菌细胞壁脂可以驱动免疫逃避，但其潜在机制尚不完全清楚。在这里，作者表明TREM2是一种模式识别受体，它结合含有非糖基化霉菌酸的脂类，并抑制Mincle诱导的抗分枝杆菌巨噬细胞反应。
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. Mycobacterial cell wall lipids can drive immunoevasion, but underlying mechanisms are incompletely understood. Here the authors show TREM2 is a pattern recognition receptor that binds non-glycosylated mycolic acid-containing lipids and inhibits Mincle-induced anti-mycobacterial macrophage responses.
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影响因子：
5.5
作者：
Boggiano C;Eichelberg K;Ramachandra L;Shea J;Ramakrishnan L;Behar S;Ernst JD;Porcelli SA;Maeurer M;Kornfeld H
通讯作者：
Kornfeld H
DOI：
10.1056/nejmoa1211851
发表时间：
2013-01-10
期刊：
The New England journal of medicine
影响因子：
--
作者：
Guerreiro R;Wojtas A;Bras J;Carrasquillo M;Rogaeva E;Majounie E;Cruchaga C;Sassi C;Kauwe JS;Younkin S;Hazrati L;Collinge J;Pocock J;Lashley T;Williams J;Lambert JC;Amouyel P;Goate A;Rademakers R;Morgan K;Powell J;St George-Hyslop P;Singleton A;Hardy J;Alzheimer Genetic Analysis Group
通讯作者：
Alzheimer Genetic Analysis Group
DOI：
10.1084/jem.20050126
发表时间：
2005-12-19
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Flores-Villanueva PO;Ruiz-Morales JA;Song CH;Flores LM;Jo EK;Montaño M;Barnes PF;Selman M;Granados J
通讯作者：
Granados J
影响因子：
4.4
作者：
Daws, MR;Sullam, PM;Seaman, WE
通讯作者：
Seaman, WE
影响因子：
32.4
作者：
Cambier CJ;O'Leary SM;O'Sullivan MP;Keane J;Ramakrishnan L
通讯作者：
Ramakrishnan L