Cardiomyocyte oxidants production may signal to T. cruzi intracellular development

Abstract

Chagas disease, caused by the protozoan parasite Trypanosoma cruzi, presents a variable clinical course, varying from asymptomatic to serious debilitating pathologies with cardiac, digestive or cardio-digestive impairment. Previous studies using two clonal T. cruzi populations, Col1.7G2 (T. cruzi I) and JG (T. cruzi II) demonstrated that there was a differential tissue distribution of these parasites during infection in BALB/c mice, with predominance of JG in the heart. To date little is known about the mechanisms that determine this tissue selection. Upon infection, host cells respond producing several factors, such as reactive oxygen species (ROS), cytokines, among others. Herein and in agreement with previous data from the literature we show that JG presents a higher intracellular multiplication rate when compared to Col1.7G2. We also showed that upon infection cardiomyocytes in culture may increase the production of oxidative species and its levels are higher in cultures infected with JG, which expresses lower levels of antioxidant enzymes. Interestingly, inhibition of oxidative stress severely interferes with the intracellular multiplication rate of JG. Additionally, upon H2O2-treatment increase in intracellular Ca2+ and oxidants were observed only in JG epimastigotes. Data presented herein suggests that JG and Col1.7G2 may sense extracellular oxidants in a distinct manner, which would then interfere differently with their intracellular development in cardiomyocytes.

Direct and Indirect Inhibition Effects of Resveratrol against Toxoplasma gondii Tachyzoites In Vitro

“…Another toxin, H 2 O 2 , used as the positive control, also failed to increase the level of ROS production but instead produced a slight decrease. Although the harm of superabundant ROS production to the parasites has largely been documented, it was nonnegligible that a moderate ROS level was also a promoter of their propagation, as argued by some researchers in reports of studies of Trypanosoma cruzi (38,39). Therefore, we conceived of the idea that the extremely low level of ROS production might be a result of the significantly elevated SOD activity induced by resveratrol in 12 h, and it undermined the physiological redox biological signaling, thereby interfering with the metabolism or proliferation ability of the parasites.…”

ROS and Trypanosoma cruzi: Fuel to infection, poison to the heart

“…(g) Trypomastigotes treated with H 2 O 2 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.…”

The Journey ofTrypanosoma cruziunder the Redox Baton

“…ROS, including mitochondrial ROS, contribute to oxidative damage that persists during the chronic stage of infection and is involved in the functional impairment of the heart [40][41][42]. Some studies show that cardiac parasite load may vary after treatment with antioxidants but depend on the animal model and the strain used [42][43][44]. In fact, Gupta and collaborators [45] demonstrated that T. cruzi infection increases ROS production in cardiomyocytes and this effect is augmented by the pro-inflammatory cytokines.…”