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

Wilbert A. Derbigny, Raymond M. Johnson, Katherine S. Toomey, Susan Ofner, Krupakar Jayarapu

Research output: Contribution to journalArticle

29 Citations (Scopus)

Abstract

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. muridaruminfected 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.

Original languageEnglish (US)
Pages (from-to)6689-6697
Number of pages9
JournalJournal of Immunology
Volume185
Issue number11
DOIs
StatePublished - Dec 1 2010

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Chlamydia muridarum
Oviducts
Epithelial Cells
Chlamydia
Chlamydia Infections
Pattern Recognition Receptors
Adaptive Immunity
Granulocyte-Macrophage Colony-Stimulating Factor
Small Interfering RNA
Interleukin-6
Macrophages
Cytokines
Ligands

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

The Chlamydia muridarum-induced IFN-β response is TLR3-dependent in murine oviduct epithelial cells. / Derbigny, Wilbert A.; Johnson, Raymond M.; Toomey, Katherine S.; Ofner, Susan; Jayarapu, Krupakar.

In: Journal of Immunology, Vol. 185, No. 11, 01.12.2010, p. 6689-6697.

Research output: Contribution to journalArticle

Derbigny, Wilbert A. ; Johnson, Raymond M. ; Toomey, Katherine S. ; Ofner, Susan ; Jayarapu, Krupakar. / The Chlamydia muridarum-induced IFN-β response is TLR3-dependent in murine oviduct epithelial cells. In: Journal of Immunology. 2010 ; Vol. 185, No. 11. pp. 6689-6697.
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