海藻糖二霉菌酸酯通过小C型凝集素样受体（Mincle）、蛋白酪氨酸磷酸酶非受体型1（SHP-1）和FcγRIIB信号通路干扰FcγR介导的吞噬体成熟。
Trehalose dimycolate interferes with FcγR-mediated phagosome maturation through Mincle, SHP-1 and FcγRIIB signalling.
作者信息
Patin Emmanuel C, Geffken Anna C, Willcocks Sam, Leschczyk Christoph, Haas Albert, Nimmerjahn Falk, Lang Roland, Ward Theresa H, Schaible Ulrich E
机构信息
Department of Immunology and Infection, Faculty of Infectious and Tropical Disease, London School of Hygiene and Tropical Medicine, London, United Kingdom.
Department of Molecular Infection Biology, Research Center Borstel, Borstel, Germany.
出版信息
PLoS One. 2017 Apr 6;12(4):e0174973. doi: 10.1371/journal.pone.0174973. eCollection 2017.
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.
结核病的病原体结核分枝杆菌（M. tuberculosis）含有丰富的细胞壁糖脂以及一种关键的毒力因子，海藻糖-6,6'-二分枝菌酸（TDM）。TDM会导致吞噬体成熟延迟，从而通过一种尚未完全明确的机制促进分枝杆菌在宿主巨噬细胞内的存活。TDM通过单核细胞诱导型C型凝集素（Mincle）发出信号，Mincle是最近发现的一种模式识别受体。在此我们表明，在Fcγ受体（FcγR）介导的吞噬作用过程中，TDM与免疫球蛋白（Ig）G调理的珠子结合后招募Mincle会干扰吞噬体成熟。此外，TDM对吞噬体成熟的调节需要含SH2结构域的肌醇多磷酸5'磷酸酶（SHP-1）和FcγRIIB，这强烈表明在吞噬体形成过程中Mincle存在抑制性的下游信号传导。总体而言，我们的研究揭示了有助于TDM毒力的重要机制。
Zotero 插件