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The Female Lower Genital Tract Is a Privileged Compartment with IL-10 Producing Dendritic Cells and Poor Th1 Immunity following Chlamydia trachomatis Infection

While a primary genital tract infection with C. trachomatis stimulates partial-protection against re-infection, it may also result in severe inflammation and tissue destruction. Here we have dissected whether functional compartments exist in the genital tract that restrict Th1-mediated protective im...

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Detalles Bibliográficos
Autores principales: Marks, Ellen, Tam, Miguel A., Lycke, Nils Y.
Formato: Texto
Lenguaje:English
Publicado: Public Library of Science 2010
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2973832/
https://www.ncbi.nlm.nih.gov/pubmed/21079691
http://dx.doi.org/10.1371/journal.ppat.1001179
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author Marks, Ellen
Tam, Miguel A.
Lycke, Nils Y.
author_facet Marks, Ellen
Tam, Miguel A.
Lycke, Nils Y.
author_sort Marks, Ellen
collection PubMed
description While a primary genital tract infection with C. trachomatis stimulates partial-protection against re-infection, it may also result in severe inflammation and tissue destruction. Here we have dissected whether functional compartments exist in the genital tract that restrict Th1-mediated protective immunity. Apart from the Th1-subset, little is known about the role of other CD4(+) T cell subsets in response to a genital tract chlamydial infection. Therefore, we investigated CD4(+) T cell subset differentiation in the genital tract using RT-PCR for expression of critical transcription factors and cytokines in the upper (UGT) and lower genital tract (LGT) of female C57BL/6 mice in response to C. trachomatis serovar D infection. We found that the Th1 subset dominated the UGT, as IFN-γ and T-bet mRNA expression were high, while GATA-3 was low following genital infection with C. trachomatis serovar D. By contrast, IL-10 and GATA-3 mRNA dominated the LGT, suggesting the presence of Th2 cells. These functional compartments also attracted regulatory T cells (Tregs) differently as increased FoxP3 mRNA expression was seen primarily in the UGT. Although IL-17A mRNA was somewhat up-regulated in the LGT, no significant change in RORγ-t mRNA expression was observed, suggesting no involvement of Th17 cells. The dichotomy between the LGT and UGT was maintained during infection by IL-10 because in IL-10-deficient mice the distinction between the two compartments was completely lost and a dramatic shift to the predominance of Th1 cells in the LGT occurred. Unexpectedly, the major source of IL-10 was CD11c(+) CD11b(+) DC, probably creating an anti-inflammatory privileged site in the LGT.
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spelling pubmed-29738322010-11-15 The Female Lower Genital Tract Is a Privileged Compartment with IL-10 Producing Dendritic Cells and Poor Th1 Immunity following Chlamydia trachomatis Infection Marks, Ellen Tam, Miguel A. Lycke, Nils Y. PLoS Pathog Research Article While a primary genital tract infection with C. trachomatis stimulates partial-protection against re-infection, it may also result in severe inflammation and tissue destruction. Here we have dissected whether functional compartments exist in the genital tract that restrict Th1-mediated protective immunity. Apart from the Th1-subset, little is known about the role of other CD4(+) T cell subsets in response to a genital tract chlamydial infection. Therefore, we investigated CD4(+) T cell subset differentiation in the genital tract using RT-PCR for expression of critical transcription factors and cytokines in the upper (UGT) and lower genital tract (LGT) of female C57BL/6 mice in response to C. trachomatis serovar D infection. We found that the Th1 subset dominated the UGT, as IFN-γ and T-bet mRNA expression were high, while GATA-3 was low following genital infection with C. trachomatis serovar D. By contrast, IL-10 and GATA-3 mRNA dominated the LGT, suggesting the presence of Th2 cells. These functional compartments also attracted regulatory T cells (Tregs) differently as increased FoxP3 mRNA expression was seen primarily in the UGT. Although IL-17A mRNA was somewhat up-regulated in the LGT, no significant change in RORγ-t mRNA expression was observed, suggesting no involvement of Th17 cells. The dichotomy between the LGT and UGT was maintained during infection by IL-10 because in IL-10-deficient mice the distinction between the two compartments was completely lost and a dramatic shift to the predominance of Th1 cells in the LGT occurred. Unexpectedly, the major source of IL-10 was CD11c(+) CD11b(+) DC, probably creating an anti-inflammatory privileged site in the LGT. Public Library of Science 2010-11-04 /pmc/articles/PMC2973832/ /pubmed/21079691 http://dx.doi.org/10.1371/journal.ppat.1001179 Text en Marks 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
Marks, Ellen
Tam, Miguel A.
Lycke, Nils Y.
The Female Lower Genital Tract Is a Privileged Compartment with IL-10 Producing Dendritic Cells and Poor Th1 Immunity following Chlamydia trachomatis Infection
title The Female Lower Genital Tract Is a Privileged Compartment with IL-10 Producing Dendritic Cells and Poor Th1 Immunity following Chlamydia trachomatis Infection
title_full The Female Lower Genital Tract Is a Privileged Compartment with IL-10 Producing Dendritic Cells and Poor Th1 Immunity following Chlamydia trachomatis Infection
title_fullStr The Female Lower Genital Tract Is a Privileged Compartment with IL-10 Producing Dendritic Cells and Poor Th1 Immunity following Chlamydia trachomatis Infection
title_full_unstemmed The Female Lower Genital Tract Is a Privileged Compartment with IL-10 Producing Dendritic Cells and Poor Th1 Immunity following Chlamydia trachomatis Infection
title_short The Female Lower Genital Tract Is a Privileged Compartment with IL-10 Producing Dendritic Cells and Poor Th1 Immunity following Chlamydia trachomatis Infection
title_sort female lower genital tract is a privileged compartment with il-10 producing dendritic cells and poor th1 immunity following chlamydia trachomatis infection
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2973832/
https://www.ncbi.nlm.nih.gov/pubmed/21079691
http://dx.doi.org/10.1371/journal.ppat.1001179
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