Functional expression of pattern recognition receptors in tissues of the human female reproductive tract

Abstract

The human female reproductive tract (FRT) must balance the requirements of procreation with the demands of protection from pathogen invasion. We hypothesize that the FRT expresses functional pattern recognition receptors (PRRs), including Toll-like Receptors (TLRs) and nucleotide-binding oligomerization domain (NOD) proteins that may mediate these tasks. Expression of PRRs was evaluated in FRT tissues by RT-PCR. PRR function within FRT tissue cells was determined by CXCL8 (IL-8) production in response to treatment with PRR agonists. We now report that TLRs 7-9 are expressed in Fallopian tube, uterine endometrium, cervix and ectocervix, while TLR10 expression is restricted to Fallopian tube. NOD1 and NOD2 and the signal transducer RICK were detected in all FRT tissues. Stimulation of FRT tissue cells with PRR ligands resulted in secretion of CXCL8. Results of these studies indicate that PRR are functionally expressed in FRT tissues, and suggest that these receptors mediate microbial recognition and immune defense in the reproductive tract.

Functional Screening of TLRs in Human Amniotic Epithelial Cells

“…Despite extensive literature on TLR expression in the female genital tract (14,17,18,26,27), little is known about the TLR repertoire and its response upon TLR ligand engagement in human amniotic epithelial cells, which represent the first line of host defense against intra-amniotic bacteria. It seems then important to determine if this final epithelial cell barrier has a specific mechanism to recognize and respond to invading pathogens.…”

New insights into pattern recognition receptors and their ligands in gynecologic pathologies

“…We review the expression of PRRs in the female reproductive tract. Several investigators have documented expression of TLRs 1-10 in tissues of the human female genital tract [24]. The vagina also expresses most of the TLRs.…”

“…Inflammatory cytokines, such as IFN-␥ and TNF-␣ induce upregulation of TLR4 expression, resulting in increased LPS responsiveness. Elevated expression of TLRs seems to be regulated by bacteria-induced inflammation [24].…”

Toll-like Receptors in Pregnancy Disorders and Placental Dysfunction

“…The remaining plasma membrane TLRs, TLR5 and TLR11, recognize bacterial flagellin and profilin, respectively [1]. TLRs 3,7,8,and 9 play key roles in the recognition of virally infected cells by detecting foreign nucleic acids to trigger the production of type I interferons [5]. TLR3 Fig.…”

“…The variety of ligands to which TLRs can respond underscores the importance of the TLR proteins in the host innate immune response. Not surprisingly, TLRs are widely expressed throughout the female reproductive tract [9], a source for many species of bacteria and other danger signals that requires an innate immune response to maintain normal function.…”