The balance of apoptotic and necrotic cell death in Mycobacterium tuberculosis infected macrophages is not dependent on bacterial virulence.
The balance of apoptotic and necrotic cell death in Mycobacterium tuberculosis infected macrophages is not dependent on bacterial virulence.
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DOI：
10.1371/journal.pone.0047573
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Stewart GR
中科院分区：
文献类型：
--
作者：
Butler RE;Brodin P;Jang J;Jang MS;Robertson BD;Gicquel B;Stewart GR
结核分枝杆菌致病的一个重要机制是能够控制感染的巨噬细胞中的细胞死亡途径：凋亡细胞死亡是杀菌的，而坏死细胞死亡可能促进细菌的传播和传播。我们使用自动共聚焦荧光显微镜、图像分析、流式细胞术、基于平板读数器的活力测定以及结核分枝杆菌菌株（包括H37 Rv）和北京谱系分离株GC 1237的等基因强毒株和无毒毒株来检查结核分枝杆菌对自发性和化学诱导的巨噬细胞死亡的控制。我们发现，细菌的毒力影响caspase激活的动力学和细胞毒性的总水平。我们发现，结核分枝杆菌抑制外源刺激的细胞凋亡的强大能力被毒力丧失所废除。然而，毒力的丧失不影响巨噬细胞凋亡和坏死的平衡-与诱导更高相对水平的凋亡的H37 Rv相比，GC 1237的毒性和无毒力等基因株均诱导主要的坏死细胞死亡。这表明在M.巨噬细胞结核感染。毒力影响宿主细胞死亡的水平和抑制细胞凋亡的能力，但其他菌株特异性特征影响宿主细胞死亡的最终模式并改变细胞凋亡和坏死的平衡。
An important mechanism of Mycobacterium tuberculosis pathogenesis is the ability to control cell death pathways in infected macrophages: apoptotic cell death is bactericidal, whereas necrotic cell death may facilitate bacterial dissemination and transmission. We examine M.tuberculosis control of spontaneous and chemically induced macrophage cell death using automated confocal fluorescence microscopy, image analysis, flow cytometry, plate-reader based vitality assays, and M.tuberculosis strains including H37Rv, and isogenic virulent and avirulent strains of the Beijing lineage isolate GC1237. We show that bacterial virulence influences the dynamics of caspase activation and the total level of cytotoxicity. We show that the powerful ability of M.tuberculosis to inhibit exogenously stimulated apoptosis is abrogated by loss of virulence. However, loss of virulence did not influence the balance of macrophage apoptosis and necrosis – both virulent and avirulent isogenic strains of GC1237 induced predominantly necrotic cell death compared to H37Rv which induced a higher relative level of apoptosis. This reveals that macrophage necrosis and apoptosis are independently regulated during M. tuberculosis infection of macrophages. Virulence affects the level of host cell death and ability to inhibit apoptosis but other strain-specific characteristics influence the ultimate mode of host cell death and alter the balance of apoptosis and necrosis.
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影响因子：
2.4
作者：
Lee J;Hartman M;Kornfeld H
通讯作者：
Kornfeld H
影响因子：
15.9
作者：
Hinchey, Joseph;Lee, Sunhee;Porcelli, Steven A.
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Chan FK
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3.4
作者：
Derrick, Steven C.;Morris, Sheldon L.
通讯作者：
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