Characterization of surface proteins and exosomes and their role in host:pathogen and parasite:parasite interactions
- Author(s): Twu, Olivia
- Advisor(s): Johnson, Patricia J
- et al.
Trichomonas vaginalis, an extracellular protozoan parasite, is the causative agent of the most common, non-viral sexually transmitted infection. Infection is often asymptomatic, but is associated with long-term effects such as premature labor, low-birth weight babies, cervical cancer, prostate cancer, and increased risk of HIV infection. In spite of its prevalence and medical importance, the pathogenesis of T. vaginalis is poorly understood. It is known that adherence to epithelial cells is vital to the establishment and maintenance of infection. This thus implicates surface and secreted proteins in host:pathogen interactions. In this study, we characterize the surface proteome of various strains of differing adherence leading to the identification of a new family of hypothetical proteins involved in attachment. The surface proteome also revealed the presence of the tetraspanin family. Characterization of one tetraspanin protein led to the discovery of small-secreted vesicles called exosomes. We demonstrate parasite exosomes are involved in host immune modulation and parasite attachment. The exosome proteome resulted in the identification of a T. vaginalis homolog of the human cytokine macrophage migration inhibitory factor (TvMIF). We show that TvMIF has immunogenic and procarcinogenic properties. Finally, we determine that an exosomal and surface localized GP63-like metalloprotease is involved in both parasite cytolysis and attachment. Taken together, our data shed light on the molecular mechanisms of pathogenesis, particularly parasite attachment, and lend novel insight into the link between T. vaginalis infection and prostate cancer. Furthermore, these data provide a strong foundation for future studies into host:pathogen interactions.