An epistatic effect of apaf-1 and caspase-9 on chlamydial infection.
An epistatic effect of apaf-1 and caspase-9 on chlamydial infection.
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DOI：
10.1007/s10495-015-1161-x
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发表时间：
2015-10
期刊：
影响因子：
--
通讯作者：
Azuma Y
中科院分区：
文献类型：
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作者：
Rahman MA;Shirai M;Aziz MA;Ushirokita R;Kubota S;Suzuki H;Azuma Y
衣原体是一种专性细胞内细菌病原体，仅在称为包涵体的膜结合空泡内复制。衣原体似乎扰乱宿主的多个细胞过程，例如，膜运输系统的重排以实现其细胞内增殖，以及抑制宿主细胞凋亡以实现持续感染。在试图澄清宿主因子参与细胞凋亡调控，我们发现，Caspase-9的抑制限制，而Apaf-1促进，肺炎衣原体感染HEp-2，HeLa和小鼠上皮成纤维细胞（MEF）。使用caspase-9−/−和apaf-1−/− MEFs证实了这些对衣原体感染的贡献。在沙眼衣原体感染的病例中也出现了类似的现象。有趣的是，apaf-1−/− MEFs中的caspase-9被衣原体感染激活，但在感染过程中caspase-3没有被激活。也就是说，胱天蛋白酶-9在没有Apaf-1的增殖和激活支持的情况下被激活，并且激活的胱天蛋白酶-9可以与胱天蛋白酶级联物理断开。这可能部分解释了衣原体包涵体内的caspase-9积累的观察。衣原体对caspase-9的隔离似乎导致细胞凋亡抑制，这对衣原体的发育周期至关重要。由于Apaf-1与细胞内先天免疫受体NOD 1共享结构域，因此它可能在调节衣原体感染的策略中发挥关键作用。
Chlamydia is an obligate intracellular bacterial pathogen that replicates solely within a membrane-bound vacuole termed an inclusion. Chlamydia seems to perturb multiple cellular processes of the host, such as, rearrangement of the membrane trafficking system for its intracellular multiplication, and inhibition of host cell apoptosis for persistent infection. In an attempt to clarify host factor involvement in apoptosis regulation, we found that inhibition of Caspase-9 restricted, while Apaf-1 promoted, Chlamydia pneumoniae infection in HEp-2, HeLa, and mouse epithelial fibroblast (MEF) cells. These opposition contributions to the chlamydial infection were confirmed using caspase-9−/− and apaf-1−/− MEFs. Similar phenomena also appeared in the case of infection with Chlamydia trachomatis. Interestingly, caspase-9 in apaf-1−/− MEFs was activated by chlamydial infection but during the infection caspase-3 was not activated. That is, caspase-9 was activated without support for multiplication and activation by Apaf-1, and the activated caspase-9 may be physically disconnected from the caspase cascade. This may be partially explained by the observation of caspase-9 accumulation within chlamydial inclusions. The sequestration of caspase-9 by chlamydia seems to result in apoptosis repression, which is crucial for the chlamydial development cycle. Because Apaf-1 shares domains with intracellular innate immune receptor NOD1, it may play a key role in the strategy to regulate chlamydial infection.