Analyses of the pathways involved in early-and late-phase induction of IFN-beta during C. Muridarum infection of oviduct epithelial cells

Sishun Hu, Kristen L. Hosey, Wilbert Derbigny

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

We previously reported that the IFN-β 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-β synthesis during Chlamydia infection of OE cells in vitro, we utilized specific inhibitory drugs to clarify the roles of IRF3 and NF-κB on both early- and late-phase C. muridarum infections. Our results showed that the pathways involved in the early-phase of IFN-β production were distinct from that in the late-phase of IFN-β 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-β; however, disruption of IRF3 activation at late times during infection had no effect. Interestingly, inhibition of NF-κB early during Chlamydia infection also had a negative effect on IFN-β 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-β synthesis late during infection. In contrast, IRF7 appears to play little or no role in the early synthesis of IFN-β during Chlamydia infection. Finally, we demonstrate that antibiotics that target chlamydial DNA replication are much more effective at reducing IFN-β synthesis during infection versus antibiotics that target chlamydial transcription. These results provide evidence that early- and late-phase IFN-β 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.

Original languageEnglish
Article numbere0119235
JournalPLoS One
Volume10
Issue number3
DOIs
StatePublished - Mar 23 2015

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Chlamydia Infections
Oviducts
oviducts
Chlamydia
epithelial cells
Epithelial Cells
Chlamydia muridarum
Infection
infection
DNA Replication
synthesis
Chemical activation
Anti-Bacterial Agents
DNA replication
DNA
Transcription
antibiotics
Transcription Factors
Feedback
Pharmaceutical Preparations

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Analyses of the pathways involved in early-and late-phase induction of IFN-beta during C. Muridarum infection of oviduct epithelial cells. / Hu, Sishun; Hosey, Kristen L.; Derbigny, Wilbert.

In: PLoS One, Vol. 10, No. 3, e0119235, 23.03.2015.

Research output: Contribution to journalArticle

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