Female reproductive tract (FRT) epithelial cells protect against potential pathogens and sexually transmitted infections. The purpose of this study was to determine if epithelial cells from the upper FRT secrete antimicrobials that inhibit reproductive tract pathogens which threaten women's health. Apical secretions from primary cultures of Fallopian tube, uterine, cervical and ectocervical epithelial cells were incubated with Neisseria gonorrhoeae, Candida albicans (yeast and hyphal forms), HIV-1, and Lactobacillus crispatus, prior to being tested for their ability to grow and/or infect target cells. Epithelial cell secretions from the upper FRT inhibit N. gonorrhoeae and both forms of Candida, as well as reduce HIV-1 (R5) infection of target cells. In contrast, none had an inhibitory effect on L. crispatus. Cytokines and chemokines analysis in uterine secretions revealed several molecules that could account for pathogen inhibition. These findings provide definitive evidence for the critical role of epithelial cells in protecting the FRT from infections, without comprising the beneficial presence of L. crispatus, which is part of the normal vaginal microflora of humans.

Problem:  Antigen presenting cells (APC) in the female reproductive tract play important roles in innate immune defense and activation of the adaptive immune responses. The objective of this study was to examine the effects of estradiol and PAMP on antigen presentation in the female reproductive tract. Method of Study:  DO11.10 T cell antigen receptor transgenic mice specific for the MHC class II‐restricted OVA323–339peptide were used to study the effects of estradiol and PAMP on antigen presentation of OVA by uterine epithelial (EC) and stromal cells as well as vaginal cells to OVA specific memory‐T cells. Results:  Estradiol inhibited antigen presentation of OVA by uterine EC, uterine stromal cells and vaginal cells to OVA specific memory‐T cells. When ovariectomized animals were treated with estradiol for 1 or 3 days, antigen presentation decreased by 20–80%. In contrast, incubation with TLR agonists increased antigen presentation by EC (Poly (I:C), Pam3Cys), stromal cells (PGN, Pam3Cys) and vaginal cells (LPS, Pam3Cys). Analysis of mRNA expression by real time RT‐PCR indicated that estradiol inhibited CD40, CD80/86 and class II in the uterus and vagina. In contrast, stimulation of antigen presentation by PAMP did not correlate with changes in costimulatory molecule mRNA expression. Conclusions:  These results indicate that APC in the uterus and vagina are responsive to estradiol, which inhibits antigen presentation and costimulatory molecule expression. These findings suggest that whereas APC in the uterus and vagina respond to TLR agonists with increased antigen presentation, which initiates an adaptive immune response, their effects appear to be at levels other than the expression of costimulatory molecules. Acknowledgement:  Supported by AI‐13541 from NIH.

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