Chlamydia inhibit host cell apoptosis by degradation of proapoptotic BH3-only proteins.
Chlamydia inhibit host cell apoptosis by degradation of proapoptotic BH3-only proteins.
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DOI：
10.1084/jem.20040402
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发表时间：
2004-10-04
影响因子：
15.3
通讯作者：
Häcker, G
中科院分区：
文献类型：
--
作者：
Fischer, SE;Vier, J;Kirschnek, S;Klos, A;Hess, S;Ying, SM;Häcker, G
衣原体是专性细胞内细菌，在宿主细胞内的液泡中复制。衣原体感染已被证明可以保护宿主细胞免受凋亡刺激。这可能对衣原体在人体细胞中繁殖的能力很重要。本研究表明，在感染过程中，对凋亡的抵抗是通过破坏促凋亡的bh3蛋白Bim/Bod、Puma和Bad来传递的。凋亡刺激在Bax/Bak线粒体激活的上游被阻断。在沙眼衣原体和肺炎衣原体感染过程中，Bim蛋白逐渐消失，但Bim mRNA无明显变化。蛋白酶体的抑制剂阻断了这种消失。感染细胞保留了对转染表达的Bim的敏感性，表明Bim消失与功能相关。在感染期间，与Bim的融合针对绿色荧光蛋白进行破坏。对截断突变体的分析表明，在衣原体感染期间，Bim中含有BH3结构域的短区域足以被破坏。与Bim一样，Puma和Bad蛋白在感染过程中消失。这些结果揭示了微生物干扰宿主细胞凋亡机制的新途径，并为衣原体感染过程中细胞抗凋亡提供了分子解释。
Chlamydia are obligate intracellular bacteria that replicate in a vacuole inside a host cell. Chlamydial infection has been shown to protect the host cell against apoptotic stimuli. This is likely important for the ability of Chlamydia to reproduce in human cells. Here we show that resistance to apoptosis is conveyed by the destruction of the proapoptotic BH3-only proteins Bim/Bod, Puma, and Bad during infection. Apoptotic stimuli were blocked upstream of the mitochondrial activation of Bax/Bak. During infection with both species, Chlamydia trachomatis and Chlamydia pneumoniae, Bim protein gradually disappeared without noticeable changes in Bim mRNA. The disappearance was blocked by inhibitors of the proteasome. Infected cells retained sensitivity to Bim expressed by transfection, indicating functional relevance of the Bim disappearance. Fusion to Bim targeted the green fluorescent protein for destruction during infection. Analysis of truncation mutants showed that a short region of Bim containing the BH3 domain was sufficient for destruction during chlamydial infection. Like Bim, Puma and Bad proteins disappeared during infection. These results reveal a novel way by which microbes can interfere with the host cell's apoptotic machinery, and provide a molecular explanation of the cellular resistance to apoptosis during infection with Chlamydia.
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影响因子：
3.6
作者：
Clausen, JD;Christiansen, G;Birkelund, S
通讯作者：
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影响因子：
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