Apoptosis-associated speck-like protein (ASC) controls Legionella pneumophila infection in human monocytes.
Apoptosis-associated speck-like protein (ASC) controls Legionella pneumophila infection in human monocytes.
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DOI：
10.1074/jbc.m110.197681
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发表时间：
2011-02-04
期刊：
影响因子：
--
通讯作者：
Amer AO
中科院分区：
文献类型：
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作者：
Abdelaziz DH;Gavrilin MA;Akhter A;Caution K;Kotrange S;Khweek AA;Abdulrahman BA;Grandhi J;Hassan ZA;Marsh C;Wewers MD;Amer AO
嗜肺军团菌引起肺炎的能力是由其逃避免疫系统并在人单核细胞及其衍生巨噬细胞内生长的能力决定的。人单核细胞对沙门氏菌有效激活caspase-1，但对嗜肺乳杆菌无效。嗜肺乳杆菌感染过程中炎性体缺乏激活的分子机制尚不清楚。对嗜肺乳杆菌感染期间人单核细胞中几种炎性体成分表达的评估显示，凋亡相关斑点样蛋白（ASC）和nod样受体NLRC4的表达在人单核细胞中显著下调。外源表达ASC维持嗜肺乳杆菌感染期间蛋白水平不变，传递caspase-1激活，限制病原菌生长。进一步用siRNA去除ASC，可改善NF-κB活化，促进嗜肺乳杆菌生长。因此，我们的数据表明嗜肺乳杆菌操纵ASC水平以逃避炎性体激活并在人单核细胞中生长。嗜肺乳杆菌通过靶向ASC，同时调节炎性体、凋亡体和NF-κB通路。
The ability of Legionella pneumophila to cause pneumonia is determined by its capability to evade the immune system and grow within human monocytes and their derived macrophages. Human monocytes efficiently activate caspase-1 in response to Salmonella but not to L. pneumophila. The molecular mechanism for the lack of inflammasome activation during L. pneumophila infection is unknown. Evaluation of the expression of several inflammasome components in human monocytes during L. pneumophila infection revealed that the expression of the apoptosis-associated speck-like protein (ASC) and the NOD-like receptor NLRC4 are significantly down-regulated in human monocytes. Exogenous expression of ASC maintained the protein level constant during L. pneumophila infection and conveyed caspase-1 activation and restricted the growth of the pathogen. Further depletion of ASC with siRNA was accompanied with improved NF-κB activation and enhanced L. pneumophila growth. Therefore, our data demonstrate that L. pneumophila manipulates ASC levels to evade inflammasome activation and grow in human monocytes. By targeting ASC, L. pneumophila modulates the inflammasome, the apoptosome, and NF-κB pathway simultaneously.