Chlamydia trachomatis infection of epithelial cells induces the activation of caspase-1 and release of mature IL-18.
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-1alpha 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.
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Department of Medical Microbiology, University of Manitoba, Winnipeg, Manitoba, Canada.
Shen
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Brunham
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D001426:Bacterial Proteins / Q000096:biosynthesis / Q000502:physiology; D020170:Caspase 1 / Q000378:metabolism* / Q000502:physiology; D061945:Caspase Inhibitors; D002460:Cell Line; D002692:Chlamydia trachomatis / Q000276:immunology*; D004789:Enzyme Activation / Q000276:immunology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004847:Epithelial Cells / Q000201:enzymology / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology*; D005347:Fibroblasts / Q000201:enzymology / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D006801:Humans; D020382:Interleukin-18 / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D014176:Protein Biosynthesis; D011498:Protein Precursors / Q000235:genetics / Q000378:metabolism; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D011506:Proteins / Q000037:antagonists & inhibitors; D012323:RNA Processing, Post-Transcriptional / Q000276:immunology; D012333:RNA, Messenger / Q000096:biosynthesis; D014407:Tumor Cells, Cultured
D001426:Bacterial Proteins; D061945:Caspase Inhibitors; D004791:Enzyme Inhibitors; D020382:Interleukin-18; D011498:Protein Precursors; D011500:Protein Synthesis Inhibitors; D011506:Proteins; D012333:RNA, Messenger; D020170:Caspase 1