Characterization of interferon epsilon mediated protection against Trichomonas vaginalis and its suppression by parasite extracellular vesicles

PROJECT SUMMARY / ABSTRACT Trichomonas vaginalis (Tv) the causative agent of trichomoniasis is the most common non-viral sexually transmitted infection (STI) with approximately 150 million new people infected annually. The continued emergence of drug resistant strains of Tv, and an emerging appreciation of the link between asymptomatic Tv infections with inflammation-driven pathologies and negative effects on reproductive health demands better understanding of this prevalent human infection. Clinically relevant infection most commonly occurs in female reproductive tract (FRT) where it must contend with the unique mucosal immune environment of the FRT. Thus, understanding how Tv subverts the host cell immune response, with a particular focus on the unique immune environment of the FRT, will be key in attempts to prevent pathogenesis by the parasite. Extracellular vesicles secreted by Tv (TvEVs) are now appreciated as one way the parasite can alter pathogenesis. The central hypothesis of this proposal is that TvEVs play a major role in suppressing host cell immune responses that would otherwise impede parasite-mediated host cell lysis a process critical for the acquisition of nutrients by this obligate extracellular parasite. To test this, I will leverage preliminary transcriptomic data showing that TvEVs down-regulate expression of a non-canonical, type I interferon, IFNε and in vitro assays showing that pretreatment of prostate and vaginal epithelial cells with IFNε is protective against Tv-mediated killing. In Aim 1, I will characterize the mechanism by which IFNε protects host cells from Tv-mediated cytolysis. In Aim 2, I will determine the mechanism by which TvEVs disrupt the type I IFN pathway. In addition to these aims, I have established a career development strategy that supports my research goals through a rigorous schedule of scientific communication workshops and trainings on grant writing, laboratory management, and laboratory mentorship. These activities are designed to help me successfully transition from my postdoctoral position to an independent researcher studying the unique immune response of the FRT to Tv.