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• W2949279747 abstract "ABSTRACT Reproductive tract pathology caused by Chlamydia trachomatis infection is an important global cause of human infertility. To better understand the mechanisms associated with Chlamydia -induced genital tract pathogenesis in humans, we used CRISPR genome editing to disrupt TLR3 function in the human oviduct epithelial (hOE) cell-line OE-E6/E7, in order to investigate the possible role(s) of TLR3 signaling in the immune response to Chlamydia . Disruption of TLR3 function in these cells significantly diminished the Chlamydia -induced synthesis of several inflammation biomarkers including IFN-β, IL-6, IL-6Ra, sIL-6Rβ (gp130), IL-8, IL-20, IL-26, IL-34, sTNF-R1, TNFSF13B, MMP-1, MMP-2, and MMP-3. In contrast, the Chlamydia -induced synthesis of CCL-5, IL-29 (IFNλ1) and IL-28A (IFNλ2) were significantly increased in the TLR3-deficient hOE cells when compared to their wild-type counterparts. Our results propose a role for TLR3 signaling in limiting the genital tract fibrosis, scarring, and chronic inflammation often associated with human chlamydial disease. Interestingly, we saw that Chlamydia infection induced the production of biomarkers associated with persistence, tumor metastasis, and autoimmunity such as soluble CD163 (sCD163), chitinase-3-like protein 1, osteopontin, and pentraxin-3 in the hOE cells; however, their expression levels were significantly dysregulated in the TLR3-deficient hOE cells. Finally, we demonstrate using the hOE cells that TLR3 deficiency resulted in an increased amount of chlamydial LPS within the Chlamydia inclusion, which is suggestive that TLR3 deficiency leads to enhanced chlamydial replication and possibly increased genital tract pathogenesis during human infection. Abbreviations hOE, human OE-E6/E7 cells; TLR3 KO, TLR3 knockout cell line; poly (I:C), Polyinosinic–polycytidylic acid sodium salt." @default.
• W2949279747 created "2019-06-27" @default.
• W2949279747 creator A5004890439 @default.
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• W2949279747 date "2019-06-24" @default.
• W2949279747 modified "2023-10-16" @default.
• W2949279747 title "TLR3 Deficiency Leads to Altered Immune Responses toChlamydia trachomatisInfection in Human Oviduct Epithelial Cells" @default.
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• W2949279747 doi "https://doi.org/10.1101/680793" @default.
• W2949279747 hasPublicationYear "2019" @default.
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