ABSTRACTTrichomonads are obligate protozoan parasites most renowned as venereal pathogens of the reproductive tract of humans and cattle. Recently, a trichomonad highly similar to bovine venerealTritrichomonas foetusbut having a unique tropism for the intestinal tract was recognized as a significant cause of colitis in domestic cats. Despite a high prevalence, worldwide distribution, and lack of consistently effective drugs for treatment of the infection, the cellular mechanisms ofT. foetuspathogenicity in the intestinal tract have not been examined. The aims of this study were to determine the pathogenic effect of felineT. foetuson porcine intestinal epithelial cells, the dependence ofT. foetuspathogenicity on adhesion ofT. foetusto the intestinal epithelium, and the identity of mediators responsible for these effects. Using anin vitrococulture approach to model felineT. foetusinfection of the intestinal epithelium, these studies demonstrate thatT. foetuspromotes a direct contact-dependent activation of intestinal epithelial cell apoptosis signaling and progressive monolayer destruction. Moreover, these pathological effects were demonstrated to be largely dependent onT. foetuscell-associated cysteine protease activity. Finally,T. foetuscysteine proteases were identified as enabling cytopathic effects by promoting adhesion ofT. foetusto the intestinal epithelium. The present studies are the first to examine the cellular mechanisms of pathogenicity ofT. foetustoward the intestinal epithelium and support further investigation of the cysteine proteases as virulence factorsin vivoand as potential therapeutic targets for ameliorating the pathological effects of intestinal trichomonosis.
Cysteine Protease Activity of Feline Tritrichomonas foetus Promotes Adhesion-Dependent Cytotoxicity to Intestinal Epithelial Cells