Trypanosoma cruzi exploitation of host cell membrane repair mechanisms aids invasion

Trypanosoma cruzi is a flagellated, intracellular parasite of mammals and the aetiological agent of the debilitating Chagas disease in humans. In order to survive in the host, T. cruzi has to invade and replicate in a variety of cell types. Parasite invasion of non-professional phagocytic cells is a complex process involving many factors. T. cruzi-mediated cytosolic Ca2+ ([Ca2+]i)-elevations result in the activation and fusion of lysosomes required for parasite invasion. An increase in [Ca2+]i also results in activation of the enzyme, calpain and the release of plasma membrane-derived vesicles (PMVs), from the host cell plasma membrane (PM). PMVs are small (0.1-<1 lmicrom in diameter), intact membrane vesicles released constitutively, or upon stimulation by most cells. The ability of T. cruzi to induce PMV production from various cell types and the activation of lysosomal exocytosis during repair of PM lesions, prompted us to investigate the role of these vesicles during parasite invasion. Here, we report that the release of PMVs, elicited by T. cruzi, causes damage to the host PM, which is then subverted by the parasite for entry before lysosomal repair. Furthermore, calpeptin, an agent that inhibits calpain activation, caused a marked reduction in PMV release, lysosome exocytosis and inhibited T. cruzi invasion. Interestingly, concanavalin A, a resealing inhibitor, failed to inhibit PMV release and parasite entry was slightly enhanced. This study adds to our knowledge on T. cruzi infection strategies and shows that the parasite takes advantage of a host cell mechanism for gaining access into the intracellular environment