Natural programmed cell death in T. cruzi epimastigotes maintained in axenic cultures

Trypanosoma cruzi, a parasitic protozoan, is the agent of Chagas' disease or American trypanosomiasis, an endemic pathology in Latin America, affecting up to 18 million people, with high public health costs. Programmed cell death (PCD) has many functions in development and tissue remodeling in metazoans. In protozoa, it could represent concomitant or alternative mechanisms for clonal selection, immune response evasion, and population size regulation. In this work, we describe the natural occurrence of PCD in T. cruzi epimastigotes during the stationary phase of growth in axenic culture or under nutrient deprivation. Thus, we have observed phosphatidylserine externalization, cellular volume decrease, caspase-like protein activity, and DNA fragmentation. Additionally, serum deprivation also induces autophagic characteristics such as monodansylcadaverine-labeled vesicles accumulation and redistribution of proteins homologous to Atg8. In agreement with our results, apoptosis may play an important role in parasite survival. Then, identification and modulation of molecular targets inducing programmed cell death in T. cruzi may lead to new potential therapeutic approaches for Chagas' disease.