<i>Trichomonas vaginalis</i> extracellular vesicles suppress IFNε-mediated responses driven by its intracellular bacterial symbiont <i>Mycoplasma hominis</i>.

Abstract

<i>Trichomonas vaginalis</i> is a common, extracellular, sexually transmitted parasite which is often found in symbiosis with the intracellular bacterium <i>Mycoplasma hominis</i> (Mh), an opportunistic pathogen of the female reproductive tract. How this symbiosis affects infection outcomes and the host cell innate immune response is poorly understood. Here, we show that infection with <i>T. vaginalis</i> in symbiosis with <i>M. hominis</i> or <i>M. hominis</i> alone triggers a noncanonical type I interferon, interferon-epsilon (IFNε), but infection with <i>T. vaginalis</i> alone does not. We also demonstrate that extracellular vesicles (TvEVs) produced by the parasite downregulate host cell IFNε, counteracting this symbiont-driven response and elevating infection. We further demonstrate that IFNε, a hormonally regulated cytokine produced in the human reproductive system, is protective against <i>T. vaginalis</i> cytoadherence and cytolysis of host cells. These studies provide insight into how a parasite and its bacterial symbiont work in concert to regulate host cell innate immune responses to drive infection.