Abstract
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.
Highlights
Chlamydia trachomatis is a gram-negative obligate-intracellular bacterium
TLR3 was the only IFN- production-capable TLR expressed by the oviduct cell lines, we were not able to determine whether TLR3 was responsible for IFN- production because the epithelial cells were unresponsive to the TLR3 ligand poly(I-C), and small interfering RNA techniques were ineffective at knocking down TLR3 expression
We have previously shown that murine oviduct epithelial cell lines do not express TLR4 and TLR7 to TLR9 by as determined by reverse transcription-PCR (RTPCR) analysis and by measuring the responses to specific TLR agonist stimulation [8]
Summary
Chlamydia trachomatis is a gram-negative obligate-intracellular bacterium. Serovars D to K, referred to as the urogenital serovars, cause genital tract infections including urethritis, salpingitis, epididymitis, prostatitis, and pelvic inflammatory disease. Murine oviduct epithelial cells lines infected by C. muridarum secrete a plethora of inflammatory cytokines [24]. Nod has recently been shown to contribute to the activation of IL-6 transcription in murine embryonic fibroblasts infected with C. muridarum [61]; Nod and Nod 2 are not associated with IFN- production [58]. TLR3, RIG-I, MDA5, and the unidentified PRR recognizing cytosolic DNA were the remaining candidate epithelial PRRs for triggering IFN- secretion in infected oviduct epithelial cells. Murine oviduct epithelial cells expressed TLR3 and upregulated TLR3 mRNA with infection but did not secrete IFN- in response to externally delivered poly(I-C), a potent TLR3 agonist [8], presumably because TLR3 was not on the cell surface.
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