L-arginine Metabolism in the Infection withTrypanosoma cruzi

Abstract

Trypanosoma cruzi is the causal agent of Chagas disease that affects 6–7 million people around the world, principally in Latin America. This disease is characterized for the presence of an acute phase in which the host immune response plays a central role in the elimination of the parasite. If the parasite is not efficiently eliminated, patients can remain asymptomatic or develop a chronic infection. One of the cells that are primarily infected with this intracellular parasite is macrophages (M ϕ ). M ϕ present a wide array of activation states with classically activated macrophages in one pole (CAM ϕ ) and alternatively activated macrophages (AAM ϕ ) in the other. One of the most important differences between these two activation states is the presence of the inducible nitric oxide synthase (iNOS or NOS2) in CAM ϕ and arginase 1 (Arg-1) in AAM ϕ ; both enzymes share the same substrate, l-arginine, and are reciprocally regulated by the action of Th1 cytokines in the case of NOS2 and Th2 cytokines in the case of Arg-1. The activation of CAM ϕ permits the production of nitric oxide (NO), highly trypanotoxic, while the activation of AAM ϕ allows the synthesis of polyamines, necessary for parasite duplication. l-arginine is a very important metabolite situated in the center between the elimination and perpetuation of T. cruzi .