The human apoptosis inhibitor NAIP induces pyroptosis in macrophages infected with Legionella pneumophila
The human apoptosis inhibitor NAIP induces pyroptosis in macrophages infected with Legionella pneumophila
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DOI：
10.1016/j.micinf.2012.03.006
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发表时间：
2012-11-01
影响因子：
5.8
通讯作者：
Miyamoto, Hiroshi
中科院分区：
文献类型：
--
作者：
Katagiri, Nanako;Shobuike, Takeo;Miyamoto, Hiroshi
人核苷酸寡聚化结构域样受体家族凋亡抑制蛋白（NAIP）通过抑制半胱天冬酶-3、-7和-9来防止凋亡。四种功能性Naip存在于鼠基因组中，每一种都与人NAIP同样相似。其中，Naip 5通过促进响应于嗜肺军团菌感染的巨噬细胞中的半胱天冬酶-1活化来诱导焦亡。然而，人NAIP对这种反应的贡献尚不清楚。为了研究人NAIP在巨噬细胞存活中的作用，我们在RAW 264.7巨噬细胞中稳定表达人NAIP。人NAIP抑制喜树碱诱导的巨噬细胞凋亡，但增强L。嗜肺菌感染的细胞这种细胞毒性与caspase-1有关。此外，人NAIP抑制L.嗜肺菌L.嗜肺菌鞭毛蛋白是细胞毒性、半胱天冬酶-1活化和限制细胞内细菌生长所必需的。鼠Naip 5的表达产生可比较的结果。这些数据表明，人NAIP调节宿主对L。人NAIP和鼠Naip 5以类似于鼠Naip 5的方式抑制嗜肺菌感染，并且人NAIP和鼠Naip 5通过抑制细胞凋亡或通过响应于特异性细胞信号促进细胞凋亡来调节细胞存活。(c)2012巴斯德研究所。由Elsevier Masson SAS出版。All rights reserved.
Human nucleotide oligomerization domain-like receptor family apoptosis inhibitory protein (NAIP) prevents apoptosis by inhibiting caspase-3, -7, and -9. Four functional Naip exist in the murine genome, each of which is equally similar to human NAIP. Among them, Naip5 induces pyroptosis by promoting caspase-1 activation in response to Legionella pneumophila infection in macrophages. However, the contribution of human NAIP to this response is unclear. To investigate the role of human NAIP in macrophage survival, we stably expressed human NAIP in RAW264.7 macrophages. Human NAIP inhibited camptothecin-induced apoptosis in macrophages; however, it promoted cytotoxicity in L. pneumophila-infected cells. This cytotoxicity was associated with caspase-1. In addition, human NAIP restricted the intracellular growth of L. pneumophila. L. pneumophila flagellin was required for cytotoxicity, caspase-1 activation, and restriction of intracellular bacterial growth. Expression of murine Naip5 produced comparable results. These data indicate that human NAIP regulates the host response to L. pneumophila infection in a manner similar to that of murine Naip5 and that human NAIP and murine Naip5 regulate cell survival by inhibiting apoptosis or by promoting pyroptosis in response to specific cellular signals. (c) 2012 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.