BID-dependent release of mitochondrial SMAC dampens XIAP-mediated immunity against Shigella
BID-dependent release of mitochondrial SMAC dampens XIAP-mediated immunity against Shigella
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DOI：
10.15252/embj.201387244
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发表时间：
2014-10-01
期刊：
影响因子：
11.4
通讯作者：
Kashkar, Hamid
中科院分区：
文献类型：
--
作者：
Andree, Maria;Seeger, Jens M.;Kashkar, Hamid
X-linked inhibitor of apoptosis protein （XIAP）是一种有效的半胱天冬酶抑制剂，以其在癌症中的抗凋亡功能而闻名。在细胞凋亡过程中，XIAP被SMAC拮抗，SMAC通过caspase介导的BID激活从线粒体中释放出来。最近的研究表明，XIAP参与免疫信号传导。在这里，我们探索XIAP作为一种重要的介质，在体外和体内对抗肠道侵袭性细菌福氏志贺氏菌的免疫反应。我们的数据首次证明志贺氏菌通过诱导线粒体中依赖于bid的SMAC释放来逃避xiap介导的免疫反应。与凋亡刺激不同，志贺氏菌激活calpain依赖性的BID裂解，触发SMAC的释放，从而拮抗XIAP的炎症作用，而不诱导细胞凋亡。我们的结果证明了细胞死亡机制如何被侵入性病原体破坏，以确保细菌定植。
The X-linked inhibitor of apoptosis protein (XIAP) is a potent caspase inhibitor, best known for its anti-apoptotic function in cancer. During apoptosis, XIAP is antagonized by SMAC, which is released from the mitochondria upon caspase-mediated activation of BID. Recent studies suggest that XIAP is involved in immune signaling. Here, we explore XIAP as an important mediator of an immune response against the enteroinvasive bacterium Shigella flexneri, both in vitro and in vivo. Our data demonstrate for the first time that Shigella evades the XIAP-mediated immune response by inducing the BID-dependent release of SMAC from the mitochondria. Unlike apoptotic stimuli, Shigella activates the calpain-dependent cleavage of BID to trigger the release of SMAC, which antagonizes the inflammatory action of XIAP without inducing apoptosis. Our results demonstrate how the cellular death machinery can be subverted by an invasive pathogen to ensure bacterial colonization.