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Analyses of the Pathways Involved in Early- and Late-phase Induction of IFN-beta During C. Muridarum Infection of Oviduct Epithelial Cells

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Journal PLoS One
Date 2015 Mar 24
PMID 25798928
Citations 5
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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.

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References
1.
Su H, Messer R, Whitmire W, FISCHER E, Portis J, Caldwell H . Vaccination against chlamydial genital tract infection after immunization with dendritic cells pulsed ex vivo with nonviable Chlamydiae. J Exp Med. 1998; 188(5):809-18. PMC: 2213383. DOI: 10.1084/jem.188.5.809. View

2.
Marie I, Durbin J, Levy D . Differential viral induction of distinct interferon-alpha genes by positive feedback through interferon regulatory factor-7. EMBO J. 1998; 17(22):6660-9. PMC: 1171011. DOI: 10.1093/emboj/17.22.6660. View

3.
Sato M, Hata N, Asagiri M, Nakaya T, Taniguchi T, Tanaka N . Positive feedback regulation of type I IFN genes by the IFN-inducible transcription factor IRF-7. FEBS Lett. 1999; 441(1):106-10. DOI: 10.1016/s0014-5793(98)01514-2. View

4.
Schaefer T, Fahey J, Wright J, Wira C . Innate immunity in the human female reproductive tract: antiviral response of uterine epithelial cells to the TLR3 agonist poly(I:C). J Immunol. 2005; 174(2):992-1002. DOI: 10.4049/jimmunol.174.2.992. View

5.
Seth R, Sun L, Ea C, Chen Z . Identification and characterization of MAVS, a mitochondrial antiviral signaling protein that activates NF-kappaB and IRF 3. Cell. 2005; 122(5):669-82. DOI: 10.1016/j.cell.2005.08.012. View