Chlamydia muridarum infection elicits a beta interferon response in murine oviduct epithelial cells dependent on interferon regulatory factor 3 and TRIF

Infect Immun. 2007 Mar;75(3):1280-90. doi: 10.1128/IAI.01525-06. Epub 2006 Dec 18.

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.

Publication types

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

MeSH terms

  • Adaptor Proteins, Vesicular Transport / physiology*
  • Animals
  • Cell Line
  • Chlamydia Infections / metabolism*
  • Chlamydia muridarum / physiology*
  • Epithelial Cells / metabolism*
  • Epithelial Cells / microbiology
  • Fallopian Tubes / cytology
  • Fallopian Tubes / metabolism
  • Fallopian Tubes / microbiology
  • Female
  • Interferon Regulatory Factor-3 / physiology*
  • Interferon-beta / biosynthesis*
  • Interferon-beta / physiology
  • Mice

Substances

  • Adaptor Proteins, Vesicular Transport
  • Interferon Regulatory Factor-3
  • Irf3 protein, mouse
  • TICAM-1 protein, mouse
  • Interferon-beta