P2X7 modulatory web in Trypanosoma cruzi infection

P2X(7) is a member of the purinergic receptors family, with extracellular adenosine triphosphate (ATP) as the main agonist, promoting cations influx and membrane permeabilization that can lead to cell death. We previously proposed that extracellular ATP is involved in thymus atrophy induced by Trypanosoma cruzi infection through the induction of CD4(+)/CD8(+) double-positive cell death and that P2X(7) could be involved in this process. To further elucidate this possibility raised by in vitro assays, in this study, we used P2X(7)(-/-) mice and observed no difference in thymus atrophy or parasitemia when compared to C57B1/6. We then decided to investigate other aspects of purinergic receptor interplay that could be better evidenced by the infection and observed that (1) thymocytes from infected and noninfected C57B1/6 mice express P2X(4) and P2X(7) receptors (Western blotting), but ATP-induced membrane permeabilization only occurs in thymocytes from infected mice; (2) peritoneal macrophages from noninfected C57B1/6 mice (P2X(4)(+) and P2X(7)(+)) are permeabilized by ATP. Although macrophages from infected C57B1/6 mice are P2X(7)(-) but P2X(4)(+), they are resistant to ATP, either through permeabilization or Ca++ influx (fluorimetry); (3) using noninfected P2X(7)(-/-) mice, C57B1/6 infected mice, and different agonistic stimuli, we observed interesting cross-talks among P2X and P2Y receptors (flow cytometry).