The Importance of TLR3 Expression and Hormonal Regulation of TLR3- Induced Immune Responses in the Human Endometrium

The human endometrium is an important site for contact between the host and pathogens ascending the reproductive tract, and thus plays an important role in female reproductive tract immunity. Toll-like receptors (TLRs) are involved in recognition of pathogens and ligation of TLRs results in the production of cytokines and chemokines important for both immune and reproductive functions of the endometrium. The reproductive tract is unique since it hormonally controls expression levels of soluble immune mediators and influx of immune cells to mediate these functions. Since TLRs have the potential to induce alterations in cytokine production through ligand recognition, TLR ligation could significantly affect endometrial health. This review focuses on the importance of TLR expression and function within the endometrium and examines the impact of steroid hormones on TLR function. The importance of TLR3 is also reviewed, as it is expressed at high levels during the window of implantation (WOI), when other TLRs and antiviral molecules are either not expressed or expressed at very low levels. Although TLR3 is not the only TLR demonstrating cycle-dependent expression, its upregulation during the WOI may indicate a unique role for TLR3 in the functioning of the endometrium and in preparation for embryo implantation.