Trypanosoma cruzi is the causative agent of Chagas’ disease, a neglected condition^[1]. The parasite is transmitted to humans by infected bugs^[2]. The disease has two distinct phases^[3]. The acute phase is characterized by the presence of the parasite in the bloodstream^[4]. During the acute phase, an effective immune response is settled to control parasite replication in the tissues^[5]. NK, T, and B cells are crucial to mediate parasite clearance through the production of interferon-γ, interleukin-17 and specific antibodies^[4-7]. Immunity cannot sterilize the host, thus leading to infection persistence and therefore, a chronic disease^[5]. The chronic illness affects mainly the heart, esophagus and large intestine^[2]. Its pathogenesis is still unclear, but a chronic inflammatory reaction in the affected organs may justify their physiological failure, that includes heart fibrosis, electrical disturbances and peristaltic movement anomalies due to peripheral neuronal destruction along with heart microvascular platelet aggregation^[8]. The genesis of the chronic inflammatory reaction is debatable. It may be induced by the persistence of the parasite in the tissues, due to an inadequate immune response or an exaggerated response as a result of missing regulatory mechanisms as an autoimmune disease^[5]. Trypanocidal drug-treatment, during the chronic phase, diminishes the parasite load but was unable to revert or to halt the development of the cardiac pathology^[9], arguing that myocardial damage may be independent of the parasite^[10].

  As mentioned above, IL-17 is crucial for the control of the acute infection^[11,12]. Its over expression induces an earlier control of parasite replication and a massive, uncontrolled inflammatory reaction that kills the host^[12]. These results are in agreement with the postulated role for IL-17 as an inflammatory cytokine^[13-15]. On the other hand, there is evidence that IL-17 may regulate Th1 responses or recruits IL-10 neutrophil producers, favoring host survival during the acute infection by the down-regulation of an exacerbated immune response^[5,16,17]. Experimental evidence concerning the role of IL-17 during the chronic phase of T. cruzi infection is missed. However, recently, two studies concerning the production and blood levels of IL-17 in Chagas patients have reported that subjects with cardiomyopathy have lower levels of IL-17 when compared with patients that were free of cardiac disease^[18,19]. Therefore, in agreement with experimental studies, the authors claim that IL-17 was a disease-protective cytokine in the chronic T. cruzi infection. Also, they have proposed that higher levels of this interleukin would be a reliable biomarker for patients that do not present any clinical signs of myocardial disease, known as the indeterminate form of the chronic Chagas’ disease^[19]. High production of IL-17 is associated with some autoimmune and inflammatory diseases, and its blockade is usually beneficial^[13]. Therefore, the protective role of IL-17 in the evolution of Chagas’ disease is rather a surprising finding, considering its possible nature as an autoimmune disease. Recently, TH-17 could not be associated with inflammatory but rather with a homeostatic/regulatory signature^[20]. This observation would favor an alternative hypothesis, and one should consider different biological functions for TH-17, depending on the producer cell-type or even the location (organ) these cells are parked. However, Chagas’ disease may include another particular situation since one of the most common drugs used to treat chagasic heart failure is digoxin, a drug reported to be a potent inhibitor of IL-17 production either in mice or humans^[21]. Information about drugs taken by chagasic patients is missed from both clinical studies mentioned above.

Conclusion

  In this opinion letter, we have briefly discussed the role of IL-17 in Chagas’ disease, proposing an alternative explanation to the fact that this interleukin was diminished in chagasic patients with established heart disease, especially in patients with congestive heart failure[19]. We argue that lower levels of IL-17 could be due to the use of digoxin intake by patients rather than a particular immune response that could favor or not the production of IL-17. Therefore, an alternative interpretation of these results may well be considered, and further studies/information is needed to clarify this point.

Conflict of interest:
  The authors declare no conflicts of interest.

References