Chlamydia trachomatis infection of epithelial cells induces the activation of caspase-1 and release of mature IL-18
Chlamydia trachomatis infection of epithelial cells induces the activation of caspase-1 and release of mature IL-18
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DOI：
10.4049/jimmunol.165.3.1463
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发表时间：
2000-08-01
影响因子：
4.4
通讯作者：
Brunham, RC
中科院分区：
文献类型：
--
作者：
Lu, H;Shen, CX;Brunham, RC
分泌 IFN-γ 的 Th1 细胞在针对包括衣原体在内的细胞内病原体的保护性免疫中特别重要，并且 IL-18 与 IL-12 一起是 CD4 T 细胞分泌 IFN-γ 的强诱导剂。由于已知上皮细胞可以合成 IL-18，因此我们研究了人上皮细胞系沙眼衣原体感染对 IL-18 分泌的影响。我们证实了几种人上皮细胞系组成型表达前IL-18，并且沙眼衣原体感染导致细胞分泌成熟的IL-18，这在沙眼衣原体的几种不同血清型和生物型中观察到。衣原体诱导的上皮细胞分泌 IL-18 在转录后水平受到调节，并且依赖于 caspase-1、IL-1 α 或来自衣原体感染的上皮细胞的其他分泌因子的激活，以及衣原体结构成分不参与诱导 IL-18 分泌。 caspase-1 的激活和成熟 IL-18 分泌的增加与衣原体相关，但与宿主蛋白质合成无关。与上皮细胞系相比，成纤维细胞系组成性表达低水平的 pro-IL-18，并且在衣原体感染后即使 caspase-1 被激活，也不分泌成熟的 IL-18。综上所述，结果表明衣原体衍生因子对于受感染上皮细胞中通过 caspase-1 激活分泌成熟 IL-18 至关重要。
Th1 cells that secrete IFN-gamma are particularly important in protective immunity against intracellular pathogens, including chlamydiae, and IL-18 together with IL-12 are strong inducers of IFN-gamma secretion by CD4 T cells. Because epithelial cells are known to synthesize IL-18, we investigated the effects of Chlamydia trachomatis infection of human epithelial cell lines on IL-18 secretion. We confirmed that several human epithelial cell lines constitutively express pro-IL-18 and that C, trachomatis infection causes cells to secrete mature IL-18, This was observed for several different serovars and biovars of C, trachomatis. Chlamydia-induced secretion of IL-18 from epithelial cells was regulated at the posttranscriptional level and was dependent on the activation of caspase-1, IL-1 alpha or other secreted factor(s) from chlamydia-infected epithelial cells as well as chlamydial structural component(s) were not involved in inducing IL-18 secretion. Activation of caspase-1 and increased secretion of mature IL-18 was correlated with chlamydial, but not with host protein synthesis. In contrast to epithelial cell lines, fibroblast cell lines constitutively expressed much lower levels of pro-IL-18 and did not secrete mature IL-18 after chlamydial infection even though caspase-1 was activated. Taken together, the results suggest that a chlamydia-derived factor(s) is essential for the secretion of mature IL-18 through caspase-1 activation in infected epithelial cells.