Chronic Chagas' Disease: Targeting the Interleukin-2 Axis and Regulatory T Cells in a Condition for Which There Is No Treatment

The intracellular protozoan parasite Trypanosoma cruzi causes Chagas’ disease in humans (Mengel and Rossi, 1992; Rassi et al., 2010). According to the latest studies, about 5–8 million people are infected by this parasite around the world, representing a significant global economic burden (Rassi et al., 2010; Lee et al., 2013; Maguire, 2015). The infection may be divided in acute, indeterminate and chronic (Mengel and Rossi, 1992; Andrade et al., 2014). The acute disease, much less frequent nowadays, may be, in most patients, successfully treated with benznidazole, a drug that efficiently kills the parasite (Rassi et al., 2010). On the other hand, the chronic disease is by far the most important condition, concerning the total number of infected people. The chronic disease is characterized by a persistent inflammatory reaction and destruction of host cells, affecting mainly the peripheral autonomous nervous system in the gastrointestinal tract, the heart muscle and intracardiac nerves in ∼30–40% of the infected patients, causing the development of megaesophagus and megacolon, and cardiomegaly associated with progressive and untreatable heart failure, in addition to an increased frequency of sudden death (Andrade et al., 2014). Yet, the majority (about 60–70%) of the patients that progress to the chronic phase remain clinically asymptomatic (Umezawa et al., 2001). Contrarily to most predictions, a large, multicentric, placebo-controlled, double-blinded clinical trial has shown that treatment with benznidazole has failed to modify the clinical outcome of chronic Chagas’ disease, in spite of promoting a significant parasite load reduction (Morillo et al., 2015). these results argue that the treatment concept fails rather than the anti-parasite effect of the drug itself, suggesting that the presence of the parasite in the chronic infectionmay not be the only factor responsible for its clinical progression but perhaps a chronic infection that is inappropriately dealt with by the host defenses would be a major question, possibly involving a malfunction of regulatory immune mechanisms and autoimmune phenomena (Mengel and Rossi, 1992; Cardillo et al., 2015). This theoretical framework also accommodatesmost chronically T. cruzi-infected patients, where this malfunction of regulatory immune mechanisms would not take place, a balanced immune response would be achieved, and pathology would not prevail (Cardillo et al., 2015).