Apoptosis is an innate defense function of macrophages against Mycobacterium tuberculosis.
Apoptosis is an innate defense function of macrophages against Mycobacterium tuberculosis.
复制标题
凋亡是巨噬细胞对结核分枝杆菌的先天防御功能。
作者：
在结核分枝杆菌（Mtb）感染的巨噬细胞死亡时，通常可观察到两种不同的死亡形式：（i）坏死，一种以细胞裂解为特征的死亡方式；（ii）凋亡，一种保持质膜完整的死亡形式。坏死是细菌离开巨噬细胞、逃避宿主防御并扩散的一种机制。相反，受感染巨噬细胞的凋亡与病原体活力降低有关。当肿瘤坏死因子激活外源性死亡结构域途径，导致半胱天冬酶 - 8激活时，就会发生凋亡。此外，还需要线粒体外膜通透性增加以激活内源性凋亡途径。这两种途径都会导致半胱天冬酶 - 3激活，从而引发凋亡。我们最近证明，在分枝杆菌感染期间，细胞死亡受类花生酸、前列腺素E2（促凋亡）和脂氧素（LX）A4（促坏死）的调节。尽管前列腺素E2可防止坏死，但有毒力的Mtb会诱导LXA4并抑制前列腺素E2的产生。在这种情况下，线粒体内膜损伤会导致巨噬细胞坏死。因此，有毒力的Mtb会破坏类花生酸对细胞死亡的调节，从而挫败巨噬细胞的先天防御机制。
Two different forms of death are commonly observed when Mycobacterium tuberculosis (Mtb)-infected macrophages die: (i) necrosis, a death modality defined by cell lysis and (ii) apoptosis, a form of death that maintains an intact plasma membrane. Necrosis is a mechanism used by bacteria to exit the macrophage, evade host defenses, and spread. In contrast, apoptosis of infected macrophages is associated with diminished pathogen viability. Apoptosis occurs when tumor necrosis factor activates the extrinsic death domain pathway, leading to caspase-8 activation. In addition, mitochondrial outer membrane permeabilization leading to activation of the intrinsic apoptotic pathway is required. Both pathways lead to caspase-3 activation, which results in apoptosis. We have recently demonstrated that during mycobacterial infection, cell death is regulated by the eicosanoids, prostaglandin E2 (proapoptotic) and lipoxin (LX)A4 (pronecrotic). Although PGE2 protects against necrosis, virulent Mtb induces LXA4 and inhibits PGE2 production. Under such conditions, mitochondrial inner membrane damage leads to macrophage necrosis. Thus, virulent Mtb subverts eicosanoid regulation of cell death to foil innate defense mechanisms of the macrophage.
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DOI：
10.1084/jem.20080767
发表时间：
2008-11-24
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Chen M;Divangahi M;Gan H;Shin DS;Hong S;Lee DM;Serhan CN;Behar SM;Remold HG
通讯作者：
Remold HG
影响因子：
4.8
作者：
Fujino, H;Xu, W;Regan, JW
通讯作者：
Regan, JW
影响因子：
4.8
作者：
Fujino, H;West, KA;Regan, JW
通讯作者：
Regan, JW
影响因子：
4.4
作者：
Chen, Minjian;Gan, Huixian;Remold, Heinz G.
通讯作者：
Remold, Heinz G.
影响因子：
30.5
作者：
Gan H;Lee J;Ren F;Chen M;Kornfeld H;Remold HG
通讯作者：
Remold HG