Trypanosoma cruzi trypomastigote infection drives TLR2-NF-κβ-iL-1β axis activation associated with systolic dysfunction in chronic Chagas cardiomyopathy

Chagas disease (CD), caused by the protozoan Trypanosoma cruzi, affects millions worldwide, with a high prevalence in Latin America, representing a significant public health burden. The transition from the asymptomatic acute phase to the chronic stage, where about 30% of individuals develop cardiomyopathy, poses a scientific challenge. This study explored the role of Toll-like receptor 2 (TLR2) and interleukin-1β (IL-1β) in the pathogenesis of systolic dysfunction in chronic Chagas cardiomyopathy (CCC). Through flow cytometry analysis of CD14 + HLA-DR+ cells, after trypomastigote infection assays, we observed higher TLR2 expression and activation in patients with preserved systolic function and systolic dysfunction (SD) compared to those without cardiac abnormalities. Notably, patients with SD exhibited higher percentages of NF-κβ + IL-1β+ cells and of mean fluorescence intensity of IL-1β in CD14 + HLA-DR + TLR2 + NF-κβ+ cells. A significant negative correlation was observed between left ventricular ejection fraction and IL-1β expression. These findings suggest that higher TLR2-mediated IL-1β production, likely through NF-κβ activation, plays a critical role in the development of systolic dysfunction in CCC. This study provides clinical evidence supporting the TLR2-NF-κβ-IL-1β axis as a potential therapeutic target for mitigating cardiac damage in CCC, considering the progression to chronic and symptomatic cases.