Oxidative stress fuels T. cruzi infection in macrophages, fibroblasts, and cardiomyocytes.

(a) Parasite burden of nonactivated C57BL/6 macrophages infected with CL-Brener (type VI) or Y strain (type II) trypomastigotes and cultivated in medium for 48 h. (b) Infected macrophages incubated with H₂O₂, PMA, or pro-oxidants have increased parasite burden [17, 27]. A similar result is obtained if parasites are treated with H₂O₂ before infection [17]. (c) Infected macrophages incubated with antioxidants have decreased parasite burden. (d) THP-1 human macrophage lineage transfected with an Nrf2- or HO-1-containing plasmid before infection presents smaller parasite burden than cells transfected with an empty expression plasmid [27]. (e) Infected gp91^phox-/- macrophages have smaller parasite burden than wild-type macrophages [17, 27]. (f) Trypomastigotes treated with H₂O₂ before infecting gp91^phox-/- macrophages give rise to parasite burden similar to that of nontreated trypomastigotes growing in wild-type macrophages, as in (a) [17]. (g) Trypomastigotes treated with H₂O₂ before infecting fibroblasts also give rise to increased parasite burden [50]. (h) Cardiomyocytes infected with the JG strain (type II) respond to CAT-PEG with decreased burden compared to nontreated cells, while cardiomyocytes infected with Col1.7G2 (type I) are unresponsive to CAT-PEG [57]. CAT-PEG, catalase conjugated to polyethylene glycol to permeate the cells; HO-1, heme oxygenase; JG, type II T. cruzi strain; Nrf2, nuclear erythroid factor-2; PMA, phorbol 12-myristate 13-acetate.