Inflammasome-dependent Caspase-1 Activation in Cervical Epithelial Cells Stimulates Growth of the Intracellular Pathogen Chlamydia trachomatis
Inflammasome-dependent Caspase-1 Activation in Cervical Epithelial Cells Stimulates Growth of the Intracellular Pathogen Chlamydia trachomatis
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DOI：
10.1074/jbc.m109.026823
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发表时间：
2009-09-25
影响因子：
4.8
通讯作者：
Ojcius, David M.
中科院分区：
文献类型：
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作者：
Abdul-Sater, Ali A.;Koo, Evonne;Ojcius, David M.
炎性小体广泛存在于单核细胞和巨噬细胞中，但不存在于上皮细胞中，而上皮细胞是许多病原体的首选宿主细胞。我们发现宫颈上皮细胞表达一个功能性炎性体。沙眼衣原体感染细胞可激活caspase-1，这一过程需要nod样受体家族成员NLRP3和炎性体接头蛋白ASC。衣原体液泡通过III型分泌装置分泌新合成的毒力蛋白，导致K+通过格列本脲敏感的K+通道外排，进而刺激活性氧的产生。在感染细胞中，活性氧水平升高是nlrp3依赖性caspase-1激活的原因。在单核细胞和巨噬细胞中，caspase-1参与促炎细胞因子如白细胞介素-1 β的加工和分泌。然而，在上皮细胞中，已知不分泌大量白细胞介素-1 β， caspase-1先前已被证明可增强脂质代谢。在这里，我们表明，在宫颈上皮细胞中，caspase-1激活是细胞内衣原体最佳生长所必需的。
Inflammasomes have been extensively characterized in monocytes and macrophages, but not in epithelial cells, which are the preferred host cells for many pathogens. Here we show that cervical epithelial cells express a functional inflammasome. Infection of the cells by Chlamydia trachomatis leads to activation of caspase-1, through a process requiring the NOD-like receptor family member NLRP3 and the inflammasome adaptor protein ASC. Secretion of newly synthesized virulence proteins from the chlamydial vacuole through a type III secretion apparatus results in efflux of K+ through glibenclamide-sensitive K+ channels, which in turn stimulates production of reactive oxygen species. Elevated levels of reactive oxygen species are responsible for NLRP3-dependent caspase-1 activation in the infected cells. In monocytes and macrophages, caspase-1 is involved in processing and secretion of pro-inflammatory cytokines such as interleukin-1 beta. However, in epithelial cells, which are not known to secrete large quantities of interleukin-1 beta, caspase-1 has been shown previously to enhance lipid metabolism. Here we show that, in cervical epithelial cells, caspase-1 activation is required for optimal growth of the intracellular chlamydiae.