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Background  Chagas disease caused by  Trypanosoma cruzi  ( T. cruzi ) affects approximately six million individuals worldwide. Clinical manifestations are expected to occur due to the parasite persistence and host immune response. Herein we investigated potential associations between  IL1B ,  IL6 ,  IL17A , or  IL18  polymorphism profiles and cardiomyopathy or  T. cruzi  parasitemia, as well as the impact of HIV infection on cardiopathy.    Methods  Two hundred twenty-six patients and 90 control individuals were analyzed.  IL1B  rs1143627 T>C,  IL6  rs1800795 C>G,  IL17A  rs2275913 G>A,  IL18  rs187238 C>G, and  IL18  rs1946518 C>A SNVs were analyzed by real-time PCR and  T. cruzi  parasitemia by PCR.    Results  Our data revealed association between a cytokine gene polymorphism and parasitemia never previously reported. The  IL6  rs1800795 CG genotype lowered the risk of positive parasitemia (OR = 0.45, 95% CI 0.24–0.86, P = 0.015). Original findings included associations between  IL17A  rs2275913 AA and  IL18  s1946518 AA genotypes with decreased risk of developing cardiomyopathy (OR = 0.27, 95% CI 0.07–0.97, P = 0.044; and OR = 0.35, 95% CI 0.14–0.87, P = 0.023, respectively).  IL18  rs1946518 AA and  IL1B  rs1143627 TC were associated with reduced risk for cardiomyopathy severity, including NYHA (New York Heart Association) class ≥ 2 (OR = 0.21, 95% CI 0.06–0.68, P = 0.009; and OR = 0.48, 95% CI 0.24–0.95, P = 0.036, respectively) and LVEF (left ventricular ejection fraction) <45% for  IL18  rs1946518 AA (OR = 0.22, 95% CI 0.05–0.89, P = 0.034). A novel, unexpected protective effect of HIV infection against development/progression of cardiomyopathy was identified, based on a lower risk of developing cardiopathy (OR = 0.48, 95% CI 0.23–0.96, P = 0.039), NYHA class ≥ 2 (OR = 0.15, 95% CI 0.06–0.39, P < 0.001), and LVEF < 45% (OR = 0.03, 95% CI 0.00–0.25, P = 0.001). Digestive involvement was negatively associated with NYHA ≥ 2 and LVEF < 45% (OR = 0.20, 95% CI 0.09–0.47, P < 0.001; and OR = 0.24, 95% CI 0.09–0.62, P = 0.004, respectively).    Conclusions  Our data support a protective role of  IL17A  AA,  IL18  AA, and  IL1B  TC genotypes against development/progression of cardiomyopathy and a modulatory effect of the  IL6  CG genotype on the risk of parasitemia in Chagas disease. Notably, HIV infection was shown to protect against development/progression of cardiopathy, potentially associated with a synergistic effect of HIV and highly active antiretroviral therapy (HAART), attenuating a Th1-mediated response in the myocardium. This proposed hypothesis requires confirmation, however, in larger and more comprehensive future studies.

frontiers in immunology

A Specific IL6 Polymorphic Genotype Modulates the Risk of Trypanosoma cruzi Parasitemia While IL18, IL17A, and IL1B Variant Profiles and HIV Infection Protect Against Cardiomyopathy in Chagas Disease