CD4+TH17 cells play a critical role in conferring resistance to Trypanosoma cruzi infection while also demonstrating potential in mitigating the development of severe cardiac complications.

Chagas disease (CD), caused by Trypanosoma cruzi, persists as a global health challenge characterized by a complex immunopathogenesis. CD4+ TH17 cells, producers of the pro-inflammatory cytokine IL-17A, have been implicated in various inflammatory and cardiac diseases, but their role in CD remains debated. This study investigated the role of TH17 IL-17A+ cells in Chagasic patients, focusing on their contribution to the immune response and cardiac protection. Our results demonstrated a distinct and potentially protective role for TH17 IL-17A+ cells in CD, particularly in the absence of dilated cardiomyopathy. In patients without systolic dysfunction, we observed an accentuated TH17 response, with elevated IL-17A expression, associated with favourable echocardiographic parameters, such as left ventricular ejection fraction (LVEF) and left ventricular end-diastolic diameter (LVDd). Furthermore, we observed an inverse correlation between IL-17A expression and intracellular parasite burden, suggesting a role for IL-17A in infection control. This study highlights the complex immunomodulatory role of TH17 cells in chronic Chagas cardiomyopathy (CCC). IL-17A may be a therapeutic target for preserving cardiac function and controlling parasite persistence in Chagasic patients, especially prior to the development of severe cardiac dysfunction.