This thin layer of fluid covers all luminal surfaces and contains multiple antimicrobial factors secreted by epithelial cells and immune cells strategically distributed throughout the

FRT. These secretions contribute in a number of ways to the defense of the FRT CCI-779 against bacterial, viral and fungal pathogens. In addition to physically protecting columnar and squamous epithelial cells that line the FRT, secretions promote ciliary clearance and contain mucus that serves both as a physical barrier and as a trap for bacteria and viruses. FRT secretions contain surfactant proteins that enhance phagocytosis of bacteria, immunoglobulins that bind bacteria, and lactoferrin that deprives bacteria of iron. Also present are antimicrobials that contribute to the protective shield against potential pathogens. As presented in this review, FRT secretions contain a spectrum of antimicrobials totaling more that 20 molecules that are able to kill or inhibit bacteria, viruses, and fungi without

inducing inflammation. Because survival depends on protection against pathogens, antimicrobial redundancy and MI-503 price synergism have evolved to provide a spectrum of protection greater than that present with a single factor.5 Less well recognized is the realization that antimicrobials in FRT tissues and secretions are under hormonal control. As a result, some antimicrobials are enhanced while others are suppressed in response to estradiol and/or progesterone. These changes lead to protection against STI at times during the menstrual cycle when aspects of the adaptive immune system are suppressed.6 Our goal in this review is to identify the innate immune cells at different sites in the FRT that provide antimicrobial protection, characterize the antimicrobials present in FRT secretions of the upper and lower FRT, and examine the changes in antimicrobials expression that occurs during the menstrual cycle, pregnancy, and following menopause. Important biologic

factors are presented under the broad headings of epithelial cells and immune cells in the FRT; antimicrobials in the upper and lower FRT; endocrine regulation of antimicrobial Progesterone protection; and relationship of antimicrobials to STI. Leukocytes in the FRT play a central role in providing cellular, humoral, and innate immune protection against bacterial and viral invasion. Using human reproductive tract tissues dispersed by enzymatic digestion prior to quantitative flow cytometry, Givan et al.7 demonstrated that CD3+ T lymphocytes were present in substantial numbers, not only in the uterine endometrium, but throughout the FRT, including the ovary, Fallopian tube, uterine endometrium, endocervix, ectocervix, and vagina.