Trehalose dimycolate interferes with FcγR-mediated phagosome maturation through Mincle, SHP-1 and FcγRIIB signalling
Trehalose dimycolate interferes with FcγR-mediated phagosome maturation through Mincle, SHP-1 and FcγRIIB signalling
复制标题
海藻糖二霉菌酸酯通过 Mincle、SHP-1 和 FcγRIIB 信号传导干扰 FcγR 介导的吞噬体成熟
作者：
Emmanuel C Patin;Anna C. Geffken;S. Willcocks;Christoph Leschczyk;A. Haas;F. Nimmerjahn;R. Lang;Theresa H Ward;U. Schaible
结核病的病原体结核分枝杆菌含有丰富的细胞壁糖脂和一个重要的毒力因子--海藻糖-6，6‘-二霉醇酸(TDM)。TDM导致吞噬小体成熟延迟，从而促进宿主巨噬细胞内分枝杆菌的存活，其机制尚不完全清楚。TDM信号通过单核细胞可诱导的C型凝集素(Mincle)，这是一种新近发现的模式识别受体。在这里，我们发现在Fcγ受体(FcγR)介导的吞噬过程中，TdM偶联免疫球蛋白(Ig)G调理小球对Mincle的募集干扰了吞噬小体的成熟。此外，TDM对吞噬小体成熟的调控需要SH2结构域的肌醇多聚磷酸5‘磷酸酶(SHP-1)和FcγRIIB，这强烈表明在吞噬小体形成过程中Mincle的下游信号被抑制。总体而言，我们的研究揭示了TDM毒力的重要机制。
The causative agent of tuberculosis, Mycobacterium tuberculosis (M. tuberculosis), contains an abundant cell wall glycolipid and a crucial virulence factor, trehalose-6,6’-dimycolate (TDM). TDM causes delay of phagosome maturation and thus promotes survival of mycobacteria inside host macrophages by a not fully understood mechanism. TDM signals through the Monocyte-INducible C-type LEctin (Mincle), a recently identified pattern recognition receptor. Here we show that recruitment of Mincle by TDM coupled to immunoglobulin (Ig)G-opsonised beads during Fcγ receptor (FcγR)-mediated phagocytosis interferes with phagosome maturation. In addition, modulation of phagosome maturation by TDM requires SH2-domain-containing inositol polyphosphate 5’ phosphatase (SHP-1) and the FcγRIIB, which strongly suggests inhibitory downstream signalling of Mincle during phagosome formation. Overall, our study reveals important mechanisms contributing to the virulence of TDM.
影响因子：
82.9
作者：
Karsten, Christian M.;Pandey, Manoj K.;Figge, Julia;Kilchenstein, Regina;Taylor, Philip R.;Rosas, Marcela;McDonald, Jacqueline U.;Orr, Selinda J.;Berger, Markus;Petzold, Dominique;Blanchard, Veronique;Winkler, Andre;Hess, Constanze;Reid, Delyth M.;Majoul, Irina V.;Strait, Richard T.;Harris, Nathaniel L.;Koehl, Gabriele;Wex, Eva;Ludwig, Ralf;Zillikens, Detlef;Nimmerjahn, Falk;Finkelman, Fred D.;Brown, Gordon D.;Ehlers, Marc;Koehl, Joerg
通讯作者：
Koehl, Joerg
影响因子：
6.4
作者：
Atul Sharma;Anthony L. Steichen;C. Jondle;B. Mishra;Jyotika Sharma
通讯作者：
Atul Sharma;Anthony L. Steichen;C. Jondle;B. Mishra;Jyotika Sharma