Elucidating the role of IFN epsilon mediated type I IFN responses against Trichomonas vaginalis - PROJECT SUMMARY / ABSTRACT Trichomonas vaginalis (Tv) is a protozoan parasite that causes the most common non-viral sexually transmitted infection (STI), trichomoniasis, world-wide. The rise in drug resistant strains of Tv, and an emerging appreciation of the link between asymptomatic Tv infections with inflammation-driven pathologies demands better understanding of this prevalent human infection. Notably, Tv infection has been linked to reproductive complications, increased susceptibility to HIV, increased incidence of cervical cancer, and increased aggressiveness of prostate cancer. Clinically relevant infection most commonly occurs in female reproductive tract (FRT) where it must contend with the unique mucosal immune environment of the FRT. Interestingly in contrast to other STIs, the detection rate of Tv is highest in peri- and post-menopausal women. 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. Over the past decade our lab has shown that extracellular vesicles secreted by Tv (TvEVs) are internalized by human cells where they can alter pathogenesis by altering cytokine secretion and increasing adherence of the parasite to its host cell. Our lab and others have also shown that neutrophils (polymorphonuclear cells [PMNs]), the major immune cell present at the Tv–host interface, kills Tv via a mechanism known as trogocytosis. Additionally, preliminary data in our lab has shown that TvEVs down-regulate expression of a non-canonical, type I interferon, IFNε and that pretreatment of prostate cells with IFNε is protective against Tv-mediated killing. Interestingly, IFNε, is known to play an important role in protection of the FRT from bacterial and viral STIs. To elucidate the role of IFNε and TvEVs we aim to: i) determine which step(s) in the IFNε-mediated type I IFN response is blocked by TvEVs and ii) determine the role of IFNε and TvEVs during Tv infection of vaginal epithelial cells and interaction with PMNs. The work proposed in this fellowship will increase our understanding of how TvEVs subvert an FRT specific immune response mediated by IFNε that would otherwise be protective against the parasite.
