Chlamydia muridarum infection elicits a beta interferon response in murine oviduct epithelial cells dependent on interferon regulatory factor 3 and TRIF.
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.
Derbigny
Wilbert A
WA
Department of Medicine, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
Hong
Soon-Cheol
SC
Kerr
Micah S
MS
Temkit
M'hamed
M
Johnson
Raymond M
RM
D033942:Adaptor Proteins, Vesicular Transport / Q000502:physiology*; D000818:Animals; D002460:Cell Line; D002690:Chlamydia Infections / Q000378:metabolism*; D023502:Chlamydia muridarum / Q000502:physiology*; D004847:Epithelial Cells / Q000378:metabolism* / Q000382:microbiology; D005187:Fallopian Tubes / Q000166:cytology / Q000378:metabolism / Q000382:microbiology; D005260:Female; D050838:Interferon Regulatory Factor-3 / Q000502:physiology*; D016899:Interferon-beta / Q000096:biosynthesis* / Q000502:physiology; D051379:Mice
D033942:Adaptor Proteins, Vesicular Transport; D050838:Interferon Regulatory Factor-3; D016899:Interferon-beta; C494233:Irf3 protein, mouse; C476286:Ticam1 protein, mouse