Chlamydia muridarum infection elicits a beta interferon response in murine oviduct epithelial cells dependent on...

Chlamydia trachomatis is the most common sexually transmitted bacterial infection in the United States. Utilizing cloned murine oviduct epithelial cell lines, we previously identified Toll-like receptor 2 (TLR2) as the principal epithelial pattern recognition receptor (PRR) for infection-triggered release of the acute inflammatory cytokines interleukin-6 and granulocyte-macrophage colony-stimulating factor. The infected oviduct epithelial cell lines also secreted the immunomodulatory cytokine beta interferon (IFN-beta) in a largely MyD88-independent manner. Although TLR3 was the only IFN-beta production-capable TLR expressed by the oviduct cell lines, we were not able to determine whether TLR3 was responsible for IFN-beta production because the epithelial cells were unresponsive to the TLR3 ligand poly(I-C), and small interfering RNA (siRNA) techniques were ineffective at knocking down TLR3 expression. To further investigate the potential role of TLR3 in the infected epithelial cell secretion of IFN-beta, we examined the roles of its downstream signaling molecules TRIF and IFN regulatory factor 3 (IRF-3) using a dominant-negative TRIF molecule and siRNA specific for TRIF and IRF-3. Antagonism of either IRF-3 or TRIF signaling significantly decreased IFN-beta production. These data implicate TLR3, or an unknown PRR utilizing TRIF, as the source of IFN-beta production by Chlamydia-infected oviduct epithelial cells.