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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

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 specifi...

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Autores principales: Hu, Sishun, Hosey, Kristen L., Derbigny, Wilbert A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4370658/
https://www.ncbi.nlm.nih.gov/pubmed/25798928
http://dx.doi.org/10.1371/journal.pone.0119235
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author Hu, Sishun
Hosey, Kristen L.
Derbigny, Wilbert A.
author_facet Hu, Sishun
Hosey, Kristen L.
Derbigny, Wilbert A.
author_sort Hu, Sishun
collection PubMed
description 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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spelling pubmed-43706582015-04-04 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 A. PLoS One Research Article 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. Public Library of Science 2015-03-23 /pmc/articles/PMC4370658/ /pubmed/25798928 http://dx.doi.org/10.1371/journal.pone.0119235 Text en © 2015 Hu et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Hu, Sishun
Hosey, Kristen L.
Derbigny, Wilbert A.
Analyses of the Pathways Involved in Early- and Late-Phase Induction of IFN-Beta during C. muridarum Infection of Oviduct Epithelial Cells
title Analyses of the Pathways Involved in Early- and Late-Phase Induction of IFN-Beta during C. muridarum Infection of Oviduct Epithelial Cells
title_full Analyses of the Pathways Involved in Early- and Late-Phase Induction of IFN-Beta during C. muridarum Infection of Oviduct Epithelial Cells
title_fullStr Analyses of the Pathways Involved in Early- and Late-Phase Induction of IFN-Beta during C. muridarum Infection of Oviduct Epithelial Cells
title_full_unstemmed Analyses of the Pathways Involved in Early- and Late-Phase Induction of IFN-Beta during C. muridarum Infection of Oviduct Epithelial Cells
title_short Analyses of the Pathways Involved in Early- and Late-Phase Induction of IFN-Beta during C. muridarum Infection of Oviduct Epithelial Cells
title_sort analyses of the pathways involved in early- and late-phase induction of ifn-beta during c. muridarum infection of oviduct epithelial cells
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4370658/
https://www.ncbi.nlm.nih.gov/pubmed/25798928
http://dx.doi.org/10.1371/journal.pone.0119235
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