The Chlamydia muridarum-induced IFN-β response is TLR3-dependent in murine oviduct epithelial cells

J Immunol. 2010 Dec 1;185(11):6689-97. doi: 10.4049/jimmunol.1001548. Epub 2010 Oct 25.


Epithelial cells lining the murine genital tract act as sentinels for microbial infection, play a major role in the initiation of the early inflammatory response, and can secrete factors that modulate the adaptive immune response when infected with Chlamydia. C. muridarum-infected murine oviduct epithelial cells secrete the inflammatory cytokines IL-6 and GM-CSF in a TLR2-dependent manner. Further, C. muridarum infection induces IFN-β synthesis in the oviduct epithelial cells in a TRIF-dependent manner. Because murine oviduct epithelial cells express TLR3 but not TLRs 4, 7, 8, or 9, we hypothesized that TLR3 or an unknown TRIF-dependent pattern recognition receptor was the critical receptor for IFN-β production. To investigate the role of TLR3 in the Chlamydia-induced IFN-β response in oviduct epithelial cells, we used small interfering RNA, dominant-negative TLR3 mutants, and TLR3-deficient oviduct epithelial cells to show that the IFN-β secreted during C. muridarum infection requires a functional TLR3. Interestingly, we demonstrate that the TLR3 signaling pathway is not required for IFN-β synthesis in C. muridarum-infected macrophages, suggesting that there are alternate and redundant pathways to Chlamydia-induced IFN-β synthesis that seem to be dependent upon the cell type infected. Finally, because there is no obvious dsRNA molecule associated with Chlamydia infection, the requirement for TLR3 in Chlamydia-induced IFN-β synthesis in infected oviduct epithelial cells implicates a novel ligand that binds to and signals through TLR3.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Bone Marrow Cells / immunology
  • Bone Marrow Cells / metabolism
  • Bone Marrow Cells / microbiology
  • Cell Line
  • Chlamydia Infections / immunology
  • Chlamydia Infections / metabolism
  • Chlamydia Infections / pathology
  • Chlamydia muridarum / immunology*
  • Clone Cells
  • Epithelial Cells / immunology*
  • Epithelial Cells / metabolism
  • Epithelial Cells / microbiology*
  • Female
  • Interferon Type I / biosynthesis*
  • Interferon Type I / metabolism
  • Ligands
  • Macrophages / immunology
  • Macrophages / metabolism
  • Macrophages / microbiology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mice, Transgenic
  • Oviducts / cytology
  • Oviducts / immunology*
  • Oviducts / metabolism
  • Oviducts / microbiology*
  • Toll-Like Receptor 3 / deficiency
  • Toll-Like Receptor 3 / metabolism
  • Toll-Like Receptor 3 / physiology*


  • Interferon Type I
  • Ligands
  • TLR3 protein, mouse
  • Toll-Like Receptor 3