The role of nitric oxide in the pathogenesis of Chagas disease.

In this chapter we summarize the protective and toxic effects of nitric oxide (NO) that are frequently seen in parallel during the infection with Trypanosoma cruzi. The killing of trypomastigotes is dependent on the production of NO which is catalyzed by the inducible NO synthase (iNOS). The cytokines IFN-gamma and TNF-alpha and several chemoatractants molecules, which act on G protein-coupled serpentine receptors, are produced during the acute infection. They play major roles in the induction of iNOS, and in the NO production-dependent killing of T. cruzi by murine macrophages. On the other hand, TGF-beta and IL-10, which are also produced during the infection, are negative regulators of NO production. In addition to mediating resistance against the infection, NO can also suppress the immune response to T. cruzi via the induction of apoptosis of T cells. Furthermore, the expression of cardiac iNOS has been associated with myocardial dysfunction. In fact, we discuss here the evidences indicating that iNOS/NO pathway is involved in the pathogenesis of neuronal and myocardial dysfunction seen in patients and in experimental models.