Benznidazole treatment reduces the induction of indoleamine 2,3-dioxygenase (IDO) enzymatic activity in Chagas disease symptomatic patients.

The enzyme indoleamine 2,3-dioxigenase (IDO) is critical for the regulation of immune responses in pro-tolerogenic antigen-presenting cell. To address the profile of immune responses associated with Chagas disease, we measured IDO activity of peripheral blood mononuclear cells from 168 chronic patients and 13 healthy donors. We found that IDO activity was increased in patients with Chagas disease when compared with controls. Moreover, the IDO activity of patients with Chagas disease in the symptomatic chronic phase, involving cardiac or digestive alterations, was higher than that detected in asymptomatic patients and correlated with the severity of the symptoms. Furthermore, benznidazole treatment induced a long-lasting decrease in IDO activity in symptomatic patients, reaching levels comparable with those of healthy donors. These results suggest that a pro-tolerogenic state is associated with the severity of Chagas disease and that benznidazole treatment is a valuable tool for breaking the parasite-driven immune tolerance in the symptomatic chronic phase of Chagas disease.