Contact-dependent cytopathogenic mechanisms of Trichomonas vaginalis.
The cytopathogenic mechanisms of Trichomonas vaginalis have been debated since the 1940s. We examined the following three proposed pathogenic mechanisms: contact-dependent extracellular killing, cytophagocytosis, and extracellular cytotoxins. Serial observations of Chinese hamster ovary (CHO) cell monolayers exposed to trichomonads revealed that (i) trichomonads form clumps, (ii) the clumps adhere to cells in culture, and (iii) monolayer destruction occurs only in areas of contact with T. vaginalis. Kinetic analysis of target cell killing by trichomonads revealed that the probability of CHO cell death was related to the probability of contact with T. vaginalis, supporting the observation by microscopy that trichomonads kill cells only by direct contact. Simultaneous studies of 111indium oxine label release from CHO cells and trypan blue dye exclusion demonstrated that T. vaginalis kills target cells without phagocytosis. Filtrates of trichomonad cultures or from media in which trichomonads were killing CHO cells had no effect on CHO cell monolayers, indicating that trichomonads do not kill cells by a cell-free or secreted cytotoxin. The microfilament inhibitor cytochalasin D (10 micrograms/ml) inhibited trichomonad killing of CHO cell monolayers by 80% (P less than 0.0001). In contrast, the microtubule inhibitor vinblastine (10(-6) M) caused only 17% inhibition of trichomonad destruction of CHO cell monolayers (P less than 0.020), whereas colchicine (10(-6) M) had no effect. T. vaginalis kills target cells by direct contact without phagocytosis. This event requires intact trichomonad microfilament function; microtubule function appears not to be essential.
D008841:Actin Cytoskeleton / Q000502:physiology; D000818:Animals; D002470:Cell Survival; D002478:Cells, Cultured; D003078:Colchicine / Q000494:pharmacology; D006224:Cricetinae; D003412:Cricetulus; D015638:Cytochalasin D; D003572:Cytochalasins / Q000494:pharmacology; D005260:Female; D006801:Humans; D007204:Indium; D008854:Microscopy, Electron; D008870:Microtubules / Q000502:physiology; D010587:Phagocytosis; D011868:Radioisotopes; D014246:Trichomonas vaginalis / Q000187:drug effects / Q000472:pathogenicity* / Q000648:ultrastructure; D014747:Vinblastine / Q000494:pharmacology
D003572:Cytochalasins; D011868:Radioisotopes; D007204:Indium; D015638:Cytochalasin D; D014747:Vinblastine; D003078:Colchicine