Cytokines, key players to turn on/off the anti-Trypanosoma cruzi innate defense mechanisms

The early host resistance against Trypanosoma cruzi infection depends on a complex interplay among cytokines, chemical mediators and cells. The major innate immune mechanism against intracellular parasites in phagocytes relies on the production of reactive oxygen species (ROS) and reactive nitrogen species (RNS). The initial step for ROS production is the generation of superoxide anion catalyzed by the enzyme NADPH oxidase. The phagocyte s NADPH oxidase is a multiprotein complex, which exists in the dissociated state in resting cells and assembles into the functional complex upon stimulation. Additionally, the high amount production of the RNS nitric oxide (NO) depends on the enzyme nitric oxide synthase induction by cytokines. The combination of superoxide anion and NO yields peroxynitrite, the most parasiteharmful reactive species. The anti-inflammatory and pro-inflammatory cytokine balance modulates the activation and induction of both enzymes. Here we discuss the cellular processes involved in macrophage-mediated host defense against Trypanosoma cruzi, and the implications of ROS, RNS and cytokine regulation in host resistance.