CD4⁺CD25⁺Foxp3⁺ regulatory T cells promote Th17 responses and genital tract inflammation upon intracellular Chlamydia muridarum infection

J Immunol. 2013 Sep 15;191(6):3430-9. doi: 10.4049/jimmunol.1301136. Epub 2013 Aug 16.


The functional role of CD4⁺CD25⁺Foxp3⁺ regulatory T cells (Tregs) in host responses to intracellular bacterial infection was investigated in an in vitro coculturing system and a murine model of Chlamydia muridarum genital tract infection. Remarkably, C. muridarum infection subverted the immune suppressive role of CD4⁺CD25⁺Foxp3⁺ Tregs; instead of hampering immune responses, Tregs not only promoted Th17 differentiation from conventional CD4⁺ T cells but also themselves converted into proinflammatory Th17 cells in both in vitro and in vivo settings. Anti-CD25 mAb PC61 treatment to deplete ∼50% of pre-existing Tregs prior to C. muridarum genital tract infection markedly reduced the frequency and the total number of Th17 but not Th1 CD4⁺ cells at both immune induction and memory phases. Most importantly, Treg-depleted mice displayed significantly attenuated inflammation, neutrophil infiltration, and reduced severity of oviduct pathology upon C. muridarum genital infection. To our knowledge, this is the first report demonstrating that the level of pre-existing CD4⁺CD25⁺Foxp3⁺ Tregs in Chlamydia-infected hosts has a major impact on the development Chlamydia-associated diseases.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Differentiation / immunology
  • Chlamydia Infections / immunology*
  • Chlamydia muridarum
  • Coculture Techniques
  • Disease Models, Animal
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Flow Cytometry
  • Immunohistochemistry
  • Inflammation / immunology
  • Lymphocyte Activation / immunology*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Reverse Transcriptase Polymerase Chain Reaction
  • T-Lymphocyte Subsets / immunology*
  • T-Lymphocytes, Regulatory / immunology*
  • Th17 Cells / immunology*