Mycobacterium tuberculosis blocks crosslinking of annexin-1 and apoptotic envelope formation on infected macrophages to maintain virulence.
Mycobacterium tuberculosis blocks crosslinking of annexin-1 and apoptotic envelope formation on infected macrophages to maintain virulence.
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DOI：
10.1038/ni.1654
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发表时间：
2008-10
影响因子：
30.5
通讯作者：
Remold HG
中科院分区：
文献类型：
--
作者：
Gan H;Lee J;Ren F;Chen M;Kornfeld H;Remold HG
感染减毒结核分枝杆菌H37Ra菌株的巨噬细胞会发生凋亡，限制细菌复制并促进抗原呈递。在此，我们证明感染H37Ra的细胞在其表面凋亡包膜形成完整后发生凋亡。这一过程需要细胞表面磷脂酰丝氨酸暴露，随后磷脂结合蛋白膜联蛋白 -1沉积，然后通过其N末端结构域由转谷氨酰胺酶介导膜联蛋白 -1交联。相反，在感染强毒株H37Rv的巨噬细胞中，膜联蛋白 -1的N末端结构域通过蛋白水解被去除，从而阻止凋亡包膜的形成，导致巨噬细胞坏死死亡。因此，强毒结核分枝杆菌的宿主防御是通过无法形成凋亡包膜而发生的，这导致巨噬细胞坏死以及肺部感染的传播。
Macrophages infected with attenuated Mycobacterium tuberculosis strain H37Ra become apoptotic, limiting bacterial replication and facilitating antigen presentation. Here, we demonstrate that cells infected with H37Ra became apoptotic after formation of an apoptotic envelope on their surface was complete. This process required exposure of phosphatidylserine on the cell surface followed by deposition of the phospholipid-binding protein annexin-1 and then transglutaminase-mediated crosslinking of annexin-1 via its N-terminal domain. In macrophages infected with virulent strain H37Rv, in contrast, the N-terminal domain of annexin-1 was removed by proteolysis thus preventing completion of the apoptotic envelope, which results in macrophage death by necrosis. Host defense of virulent Mycobacterium tuberculosis thus occurs by failure to form the apoptotic envelope, which leads to macrophage necrosis and dissemination of infection in the lung.