Novel strategies are needed to prevent and treat sexually transmitted infections. The alpha and beta defensins are a family of small, cysteine-rich peptides that are expressed in mammalian neutrophils and epithelial cells, and which exhibit antimicrobial activity against a wide range of bacteria, fungi and enveloped viruses. Human defensin-5 (HD-5) is a novel member of the a-defensin family which to date has only been found in the Paneth cells of the small intestine. The investigators recently detected a HD-5 homologue in the epithelial cells of the human female genital tract. They have demonstrated that HD-5 is differentially expressed in different regions of the tract and that expression is altered by inflammatory processes and by the stage of the menstrual cycle. The experiments outlined in this proposal will test the following hypotheses: (a) expression of HD-5 in female genital tract epithelia is upregulated by sexually transmitted pathogens, proinflammatory cytokines, and female reproductive hormones (b) HD-5 is secreted into the genital tract lumen, (c) HD-5 has effective microbicidal properties against common sexually transmitted organisms, and (d) HD-5 is a chemoattractant for leukocytes. This research will help elucidate the role of defensins at genital tract mucosal surfaces, and may facilitate the development of novel prophylactic and therapeutic agents against sexually transmitted pathogens which are based on these endogenous antibiotic peptides.
