Direct recognition of the mycobacterial glycolipid, trehalose dimycolate, by C-type lectin Mincle.
Direct recognition of the mycobacterial glycolipid, trehalose dimycolate, by C-type lectin Mincle.
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C 型凝集素 Mincle 直接识别分枝杆菌糖脂、海藻糖二霉菌酸酯。
DOI：
10.1084/jem.20091750
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发表时间：
2009-12-21
影响因子：
15.3
通讯作者：
Yamasaki, Sho
中科院分区：
文献类型：
--
作者：
Ishikawa, Eri;Ishikawa, Tetsuaki;Morita, Yasu S.;Toyonaga, Kenji;Yamada, Hisakata;Takeuchi, Osamu;Kinoshita, Taroh;Akira, Shizuo;Yoshikai, Yasunobu;Yamasaki, Sho
结核病仍然是一种由结核分枝杆菌引起的致命疾病，它含有影响宿主免疫系统的各种独特成分。海藻糖-6，6‘-二聚乙醇酸(TDM；又称脐带因子)是一种分枝杆菌细胞壁糖脂，是目前研究最多的结核分枝杆菌免疫刺激成分。尽管对TDM进行了50年的研究，但其宿主受体尚未明确确定。在这里，我们证明巨噬细胞诱导的C型凝集素(Mincle)是TDM的重要受体。热灭活的分枝杆菌激活了Mincle表达细胞，但在细菌脱脂后失去了活性；对脂类提取物的分析证实TDM是Mincle配体。TDM激活巨噬细胞产生炎性细胞因子和一氧化氮，而在Mincle缺陷的巨噬细胞中，这两种物质完全被抑制。在体内，TDM可诱导血清中炎性细胞因子的显著升高和典型的肺部炎症，如肉芽肿的形成。然而，Mincle缺陷小鼠没有形成TDM诱导的肺肉芽肿。即使在MyD88缺失的背景下，整个分枝杆菌也能够激活巨噬细胞，而Mincle/MyD88双缺失的巨噬细胞的激活作用明显减弱。这些结果表明Mincle是分枝杆菌糖脂TDM的重要受体。
Tuberculosis remains a fatal disease caused by Mycobacterium tuberculosis, which contains various unique components that affect the host immune system. Trehalose-6,6′-dimycolate (TDM; also called cord factor) is a mycobacterial cell wall glycolipid that is the most studied immunostimulatory component of M. tuberculosis. Despite five decades of research on TDM, its host receptor has not been clearly identified. Here, we demonstrate that macrophage inducible C-type lectin (Mincle) is an essential receptor for TDM. Heat-killed mycobacteria activated Mincle-expressing cells, but the activity was lost upon delipidation of the bacteria; analysis of the lipid extracts identified TDM as a Mincle ligand. TDM activated macrophages to produce inflammatory cytokines and nitric oxide, which are completely suppressed in Mincle-deficient macrophages. In vivo TDM administration induced a robust elevation of inflammatory cytokines in sera and characteristic lung inflammation, such as granuloma formation. However, no TDM-induced lung granuloma was formed in Mincle-deficient mice. Whole mycobacteria were able to activate macrophages even in MyD88-deficient background, but the activation was significantly diminished in Mincle/MyD88 double-deficient macrophages. These results demonstrate that Mincle is an essential receptor for the mycobacterial glycolipid, TDM.
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影响因子：
15.3
作者：
Geijtenbeek, TBH;van Vliet, SJ;Koppel, EA;Sanchez-Hernandez, M;Vandenbroucke-Grauls, CMJE;Appelmelk, B;van Kooyk, Y
通讯作者：
van Kooyk, Y
影响因子：
2.8
作者：
Indrigo, J;Hunter, RL;Actor, JK
通讯作者：
Actor, JK
影响因子：
56.9
作者：
Moody, DB;Reinhold, BB;Porcelli, SA
通讯作者：
Porcelli, SA
DOI：
10.1016/0006-3002(56)90289-x
发表时间：
1956-01-01
期刊：
BIOCHIMICA ET BIOPHYSICA ACTA
影响因子：
--
作者：
NOLL, H;BLOCH, H;LEDERER, E
通讯作者：
LEDERER, E
人类巨噬细胞甘露糖受体指导结核分枝杆菌脂肪氨基氨基甘氨酸介导的吞噬体生物发生。
DOI：
10.1084/jem.20051239
发表时间：
2005-10-03
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Kang PB;Azad AK;Torrelles JB;Kaufman TM;Beharka A;Tibesar E;DesJardin LE;Schlesinger LS
通讯作者：
Schlesinger LS