Surface and secreted factors modulate interactions between host cells and the parasite Trichomonas vaginalis

PATRICIA J. JOHNSON; NATALIA DE MIGUEL; OLIVIA TWU; ANGELICA RIESTRA; CHRISTOPHER RYAN

Mar del Plata

Congreso; IX Congreso Argentino de Protozoología y Enfermedades Parasitarias; 2011

Sociedad Argentina de Parasitologia

Trichomonas vaginalis is an obligate extracellular parasite that colonizes the human urogenital tract and causes the most prevalent non-viral sexually-transmitted infection worldwide. Despite being of critical importance for survival, the mechanisms used to establish an infection and thrive within the host are poorly defined. Both complex glycoconjugates and proteins on the parasite’s surface have been implicated in adherence and cytotoxicity to host cells. We have determined the structure of the major surface glycan and identified its sugar determinants that mediate the binding of this glycan to host cell galectin receptors. We have also defined the surface proteome of 6 strains of T. vaginalis with differing adherence capacities to vaginal epithelial cells, identifying 11 of 411 proteins that are 2-40X more abundant on the surface of highly adherent strains. Two tetraspanin (TSP) proteins on the flagella, plasma membrane and/or exosomes that modulate host:pathogen interactions have been examined. TSP6 was found to be a flagellar protein that redistributes to the plasma membrane when the parasite initially contacts host cells and subsequently returns to the flagella. Both targeting to the flagella and redistribution is dependent on a short C-terminal cytoplasmic tail that additionally influences the ability of the parasite to migrate through the extracellular matrix. A related protein, TSP1, has been shown to reside in large multivesicular bodies that accumulate upon contact of the parasite with vaginal epithelial cells as well as exosomes that are extruded from the parasite. T. vaginalis exosomes contain conserved exosomal proteins, ones that are uniquely found in the parasite and a specific subset of T. vaginalis small RNAs. Exosomes secreted from the parasite appear to deliver parasite proteins to host cell via fusion. Our studies also reveal that exosomes increase parasite adherence to vaginal epithelial cells, modulate immune responses and allow for cross-talk between parasites.