title: The female lower genital tract is a privileged compartment with IL-10 producing dendritic cells and poor Th1 immunity following Chlamydia trachomatis infection.
abstract: 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.
authors.affiliation: Department of Microbiology and Immunology, Mucosal Immunobiology and Vaccine Center, Institute of Biomedicine, The University of Gothenburg, Gothenburg, Sweden.
authors.forename: Ellen
authors.initials: E
authors.lastname: Marks
authors.forename: Miguel A
authors.initials: MA
authors.lastname: Tam
authors.forename: Nils Y
authors.initials: NY
authors.lastname: Lycke
mesh_terms: D000818:Animals; D015153:Blotting, Western; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D002460:Cell Line; D002690:Chlamydia Infections / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D002692:Chlamydia trachomatis / Q000276:immunology*; D016207:Cytokines / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005836:Genitalia, Female / Q000276:immunology*; D006801:Humans; D007111:Immunity, Cellular; D007124:Immunoenzyme Techniques; D016753:Interleukin-10 / Q000378:metabolism*; D007668:Kidney / Q000166:cytology / Q000821:virology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D018417:Th1 Cells / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D058504:Th17 Cells / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D018418:Th2 Cells / Q000276:immunology / Q000382:microbiology / Q000473:pathology
chemical_list: D016207:Cytokines; D012333:RNA, Messenger; D016753:Interleukin-10