Analyses of the Pathways Involved in Early- and Late-Phase Induction of IFN-Beta during C. muridarum Infection of Oviduct Epithelial Cells

作者：Hu, Sishun; Hosey, Kristen L.; Derbigny, Wilbert A.^*

来源：PLos One, 2015, 10(3): e0119235.

DOI：10.1371/journal.pone.0119235

• NF-KAPPA-B
• ALPHA/BETA-INTERFERON GENES
• CHLAMYDIA-PNEUMONIAE
• POSITIVE FEEDBACK
• GAMMA
• RECOGNITION
• ACTIVATION
• RNA
• SECRETION
• PROTEIN

We previously reported that the IFN-beta secreted by Chlamydia muridarum-infected murine oviduct epithelial cells (OE cells) was mostly dependent on the TLR3 signaling pathway. To further characterize the mechanisms of IFN-beta synthesis during Chlamydia infection of OE cells in vitro, we utilized specific inhibitory drugs to clarify the roles of IRF3 and NF-kappa B on both early-and late-phase C. muridarum infections. Our results showed that the pathways involved in the early-phase of IFN-beta production were distinct from that in the late-phase of IFN-beta production. Disruption of IRF3 activation using an inhibitor of TBK-1 at early-phase Chlamydia infection had a significant impact on the overall synthesis of IFN-beta; however, disruption of IRF3 activation at late times during infection had no effect. Interestingly, inhibition of NF-kappa B early during Chlamydia infection also had a negative effect on IFN-beta production; however, its impact was not significant. Our data show that the transcription factor IRF7 was induced late during Chlamydia infection, which is indicative of a positive feedback mechanism of IFN-beta synthesis late during infection. In contrast, IRF7 appears to play little or no role in the early synthesis of IFN-beta during Chlamydia infection. Finally, we demonstrate that antibiotics that target chlamydial DNA replication are much more effective at reducing IFN-beta synthesis during infection versus antibiotics that target chlamydial transcription. These results provide evidence that early-and late-phase IFN-beta production have distinct signaling pathways in Chlamydia-infected OE cells, and suggest that Chlamydia DNA replication might provide a link to the currently unknown chlamydial PAMP for TLR3.

• 出版日期2015-3-23
• 单位华中农业大学