title: Identifying a role for Toll-like receptor 3 in the innate immune response to Chlamydia muridarum infection in murine oviduct epithelial cells.
abstract: Because epithelial cells are the major cell type productively infected with Chlamydia during genital tract infections, the overall goal of our research was to understand the contribution of infected epithelial cells to the host defense. We previously showed that Toll-like receptor 3 (TLR3) is the critical pattern recognition receptor in oviduct epithelial (OE) cells that is stimulated during Chlamydia infection, resulting in the synthesis of beta interferon (IFN-β). Here, we present data that implicates TLR3 in the expression of a multitude of other innate-inflammatory immune modulators including interleukin-6 (IL-6), CXCL10, CXCL16, and CCL5. We demonstrate that Chlamydia-induced expression of these cytokines is severely disrupted in TLR3-deficient OE cells, whereas Chlamydia replication in the TLR3-deficient cells is more efficient than in wild-type OE cells. Pretreatment of the TLR3-deficient OE cells with 50 U of IFN-β/ml prior to infection diminished Chlamydia replication and restored the ability of Chlamydia infection to induce IL-6, CXCL10, and CCL5 expression in TLR3-deficient OE cells; however, CXCL16 induction was not restored by IFN-β preincubation. Our findings were corroborated in pathway-focused PCR arrays, which demonstrated a multitude of different inflammatory genes that were defectively regulated during Chlamydia infection of the TLR3-deficient OE cells, and we found that some of these genes were induced only when IFN-β was added prior to infection. Our OE cell data implicate TLR3 as an essential inducer of IFN-β and other inflammatory mediators by epithelial cells during Chlamydia infection and highlight the contribution of TLR3 to the inflammatory cytokine response.
authors: Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, IN, USA. wderbign@iupui.edu
authors: Wilbert A
authors: WA
authors: Derbigny
authors: LaTasha R
authors: LR
authors: Shobe
authors: Jasmine C
authors: JC
authors: Kamran
authors: Katherine S
authors: KS
authors: Toomey
authors: Susan
authors: S
authors: Ofner
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D002690:Chlamydia Infections / Q000276:immunology; D023502:Chlamydia muridarum / Q000276:immunology*; D016207:Cytokines / Q000378:metabolism*; D004847:Epithelial Cells / Q000276:immunology*; D005260:Female; D020869:Gene Expression Profiling; D007113:Immunity, Innate; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010057:Oviducts / Q000276:immunology*; D051196:Toll-Like Receptor 3 / Q000172:deficiency / Q000276:immunology*
chemical_list: D016207:Cytokines; C519703:TLR3 protein, mouse; D051196:Toll-Like Receptor 3