Analysis of the Effects of Toll‐like Receptor 3 (TLR3) on the Pathology of Chlamydia muridarum in the Genital Tract of Wild‐Type and TLR3 Knockout C57BL/6N Mice

In 2017, a total 1,708,569 chlamydial infections were reported to Centers for Disease Control and Prevention; the most prevalent sexually transmitted disease (STD). Chlamydia trachomatis primarily replicates in epithelial cells lining the reproductive tract. Epithelial cells recognize chlamydia through cell surface and cytosolic receptors, and/or endosomal innate receptors such as Toll‐like receptors (TLRs). The activation of these receptors triggers immune mechanisms that are required for chlamydial clearance. It was previously shown that Chlamydia muridarum (Cm) induces IFN‐β in oviduct epithelial cells in a TLR3‐dependent manner. TLR3's regulation of inflammatory chemicals involved in host defense against Cm infection led to the hypothesis that TLR3 plays a protective role against Cm‐induced genital tract pathology in congenic C57BL/6N mice. To test this hypothesis, wild‐type and TLR3‐deficient mice were treated with vehicle and Cm by swabbing the vaginal vault and cervix. Tissues were extracted from mice sacrificed on day 7, 21, or 42 post‐infection and fixed in 4% paraformaldehyde for 48 hrs. Paraffin‐embedded, 4‐μm sections containing cervix and both uterine horns and oviducts were stained with H&E. Genital tract sections (cervix, uterine body and horns, and oviducts) were microscopically examined and graded for the presence of acute inflammation (neutrophilic infiltrates), chronic inflammation (lymphocytic infiltrates), epithelial erosion and disruption, and luminal distension of uterine horns and oviducts using a semi qualitative pathology assessment. Inflammatory cell infiltrates, epithelial erosion and disruption were scored as follows: 0, normal; 1, mild; 2, moderate; 3, severe. All scoring was performed in a double‐blinded fashion with regards to the treatment groups. The results revealed an inflammatory immune response showing minute differences in both groups at day 7 (acute inflammation) in the oviducts, cervix and uterus. By day 21 (chronic inflammation), there was more inflammation seen in the WT group compared to the knock out TLR3 group. By day 42, there was mild chronic inflammation in the uterus in both groups; however, the knockout group had more cystic endometrial change in the uterus compared to the wild type group. In conclusion, the data suggest that TLR3 may promote the clearance of Cm. This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .