The Chlamydia muridarum-induced IFN-β response is TLR3-dependent in murine oviduct epithelial cells.
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. muridarum-infected 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.
Derbigny
Wilbert A
WA
Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, IN 46202, USA. wderbign@iupui.edu
Johnson
Raymond M
RM
Toomey
Katherine S
KS
Ofner
Susan
S
Jayarapu
Krupakar
K
D000818:Animals; D001854:Bone Marrow Cells / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D002460:Cell Line; D002690:Chlamydia Infections / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D023502:Chlamydia muridarum / Q000276:immunology*; D002999:Clone Cells; D004847:Epithelial Cells / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology*; D005260:Female; D007370:Interferon Type I / Q000096:biosynthesis* / Q000378:metabolism; D008024:Ligands; D008264:Macrophages / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D010057:Oviducts / Q000166:cytology / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology*; D051196:Toll-Like Receptor 3 / Q000172:deficiency / Q000378:metabolism / Q000502:physiology*
D007370:Interferon Type I; D008024:Ligands; C519703:TLR3 protein, mouse; D051196:Toll-Like Receptor 3