Toll-like receptor 3 (TLR3) promotes the resolution of Chlamydia muridarum genital tract infection in congenic C57BL/6N mice

Chlamydia trachomatis urogenital serovars primarily replicate in epithelial cells lining the reproductive tract. Epithelial cells recognize Chlamydia through cell surface and cytosolic receptors, and/or endosomal innate receptors such as Toll-like receptors (TLRs). Activation of these receptors trig...

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Autores principales: Carrasco, Sebastian E., Hu, Sishun, Imai, Denise M., Kumar, Ramesh, Sandusky, George E., Yang, X. Frank, Derbigny, Wilbert A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5889059/
https://www.ncbi.nlm.nih.gov/pubmed/29624589
http://dx.doi.org/10.1371/journal.pone.0195165
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author Carrasco, Sebastian E.
Hu, Sishun
Imai, Denise M.
Kumar, Ramesh
Sandusky, George E.
Yang, X. Frank
Derbigny, Wilbert A.
author_facet Carrasco, Sebastian E.
Hu, Sishun
Imai, Denise M.
Kumar, Ramesh
Sandusky, George E.
Yang, X. Frank
Derbigny, Wilbert A.
author_sort Carrasco, Sebastian E.
collection PubMed
description Chlamydia trachomatis urogenital serovars primarily replicate in epithelial cells lining the reproductive tract. Epithelial cells recognize Chlamydia through cell surface and cytosolic receptors, and/or endosomal innate receptors such as Toll-like receptors (TLRs). Activation of these receptors triggers both innate and adaptive immune mechanisms that are required for chlamydial clearance, but are also responsible for the immunopathology in the reproductive tract. We previously demonstrated that Chlamydia muridarum (Cm) induces IFN-β in oviduct epithelial cells (OE) in a TLR3-dependent manner, and that the synthesis of several cytokines and chemokines are diminished in Cm-challenged OE derived from TLR3(-/-) 129S1 mice. Furthermore, our in vitro studies showed that Cm replication in TLR3(-/-) OE is more efficient than in wild-type OE. Because TLR3 modulates the release inflammatory mediators involved in host defense during Cm infection, we hypothesized that TLR3 plays a protective role against Cm-induced genital tract pathology in congenic C57BL/6N mice. Using the Cm mouse model for human Chlamydia genital tract infections, we demonstrated that TLR3(-/-) mice had increased Cm shedding during early and mid-stage genital infection. In early stage infection, TLR3(-/-) mice showed a diminished synthesis of IFN-β, IL-1β, and IL-6, but enhanced production of IL-10, TNF-α, and IFN-γ. In mid-stage infection, TLR3(-/-) mice exhibited significantly enhanced lymphocytic endometritis and salpingitis than wild-type mice. These lymphocytes were predominantly scattered along the endometrial stroma and the associated smooth muscle, and the lamina propria supporting the oviducts. Surprisingly, our data show that CD4(+) T-cells are significantly enhanced in the genital tract TLR3(-/-) mice during mid-stage Chlamydial infection. In late-stage infections, both mouse strains developed hydrosalpinx; however, the extent of hydrosalpinx was more severe in TLR3(-/-) mice. Together, these data suggest that TLR3 promotes the clearance of Cm during early and mid-stages of genital tract infection, and that loss of TLR3 is detrimental in the development hydrosalpinx.
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spelling pubmed-58890592018-04-20 Toll-like receptor 3 (TLR3) promotes the resolution of Chlamydia muridarum genital tract infection in congenic C57BL/6N mice Carrasco, Sebastian E. Hu, Sishun Imai, Denise M. Kumar, Ramesh Sandusky, George E. Yang, X. Frank Derbigny, Wilbert A. PLoS One Research Article Chlamydia trachomatis urogenital serovars primarily replicate in epithelial cells lining the reproductive tract. Epithelial cells recognize Chlamydia through cell surface and cytosolic receptors, and/or endosomal innate receptors such as Toll-like receptors (TLRs). Activation of these receptors triggers both innate and adaptive immune mechanisms that are required for chlamydial clearance, but are also responsible for the immunopathology in the reproductive tract. We previously demonstrated that Chlamydia muridarum (Cm) induces IFN-β in oviduct epithelial cells (OE) in a TLR3-dependent manner, and that the synthesis of several cytokines and chemokines are diminished in Cm-challenged OE derived from TLR3(-/-) 129S1 mice. Furthermore, our in vitro studies showed that Cm replication in TLR3(-/-) OE is more efficient than in wild-type OE. Because TLR3 modulates the release inflammatory mediators involved in host defense during Cm infection, we hypothesized that TLR3 plays a protective role against Cm-induced genital tract pathology in congenic C57BL/6N mice. Using the Cm mouse model for human Chlamydia genital tract infections, we demonstrated that TLR3(-/-) mice had increased Cm shedding during early and mid-stage genital infection. In early stage infection, TLR3(-/-) mice showed a diminished synthesis of IFN-β, IL-1β, and IL-6, but enhanced production of IL-10, TNF-α, and IFN-γ. In mid-stage infection, TLR3(-/-) mice exhibited significantly enhanced lymphocytic endometritis and salpingitis than wild-type mice. These lymphocytes were predominantly scattered along the endometrial stroma and the associated smooth muscle, and the lamina propria supporting the oviducts. Surprisingly, our data show that CD4(+) T-cells are significantly enhanced in the genital tract TLR3(-/-) mice during mid-stage Chlamydial infection. In late-stage infections, both mouse strains developed hydrosalpinx; however, the extent of hydrosalpinx was more severe in TLR3(-/-) mice. Together, these data suggest that TLR3 promotes the clearance of Cm during early and mid-stages of genital tract infection, and that loss of TLR3 is detrimental in the development hydrosalpinx. Public Library of Science 2018-04-06 /pmc/articles/PMC5889059/ /pubmed/29624589 http://dx.doi.org/10.1371/journal.pone.0195165 Text en © 2018 Carrasco 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 (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Carrasco, Sebastian E.
Hu, Sishun
Imai, Denise M.
Kumar, Ramesh
Sandusky, George E.
Yang, X. Frank
Derbigny, Wilbert A.
Toll-like receptor 3 (TLR3) promotes the resolution of Chlamydia muridarum genital tract infection in congenic C57BL/6N mice
title Toll-like receptor 3 (TLR3) promotes the resolution of Chlamydia muridarum genital tract infection in congenic C57BL/6N mice
title_full Toll-like receptor 3 (TLR3) promotes the resolution of Chlamydia muridarum genital tract infection in congenic C57BL/6N mice
title_fullStr Toll-like receptor 3 (TLR3) promotes the resolution of Chlamydia muridarum genital tract infection in congenic C57BL/6N mice
title_full_unstemmed Toll-like receptor 3 (TLR3) promotes the resolution of Chlamydia muridarum genital tract infection in congenic C57BL/6N mice
title_short Toll-like receptor 3 (TLR3) promotes the resolution of Chlamydia muridarum genital tract infection in congenic C57BL/6N mice
title_sort toll-like receptor 3 (tlr3) promotes the resolution of chlamydia muridarum genital tract infection in congenic c57bl/6n mice
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5889059/
https://www.ncbi.nlm.nih.gov/pubmed/29624589
http://dx.doi.org/10.1371/journal.pone.0195165
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