Intracellular cyclic AMP levels modulate differential adaptive responses on epimastigotes and cell culture trypomastigotes of Trypanosoma cruzi

Abstract

Among the many environmental challenges the parasiteTrypanosoma cruzihas to overcome to complete its lifecycle through different hosts, oxidative stress plays a central role. Different stages of this parasite encounterdistinct sources of oxidative stress, such as the oxidative burst of the immune system, or the Heme released fromhemoglobin degradation in the triatomine´s midgut. Also, the redox status of the surroundings functions as asignal to the parasite, triggering processes coupled to differentiation or proliferation. Intracellular secondmessengers, like cAMP, are responsible for the transduction of environmental queues and initiating cellularprocesses accordingly. In trypanosomatids cAMP is involved in a variety of processes, including proliferation,differentiation, osmoregulation and quorum sensing. Trypanosomatid phosphodiesterases (PDE) show atypicalpharmacological properties and some have been involved in key processes for the survival of the parasites, whichvalidates them as attractive therapeutic targets. Our work here shows that cAMP modulates different processesaccording to parasite stage. Epimastigotes become more resistant to oxidative stress when pre-treated with cAMPanalogs, while in trypomastigotes an increase in intracellular cAMP doesn´t seem to aid in this response, althoughit does increase the number of amastigotes obtained 48 h after infection, compared to the control group. Also, weshow that TcrPDEA1, a functionally enigmatic phosphodiesterase with very high Km, is involved in the epi-mastigotes response to oxidative stress.