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

Abstract

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

Trypanosoma cruzi Dysregulates piRNAs Computationally Predicted to Target IL-6 Signaling Molecules During Early Infection of Primary Human Cardiac Fibroblasts

“…1B ). Other studies suggested that disruption of IL-6 expression and downstream targets during parasite infection play important roles in T. cruzi pathogenesis ( 5 6 7 47 ). These results suggest that these piRNAs may be important modulators of IL6 and SOCS3 gene expression during the early/acute phase of T. cruzi infection and pathogenesis.…”

“…Thus, there is a need to understand the molecular mechanisms of T. cruzi pathogenesis to facilitate identification of biomarkers and new therapeutic targets. The IL-6 signaling pathway has been suggested to play important roles in experimental and clinical T. cruzi pathogenesis ( 5 6 7 ). IL-6 is a cytokine with diverse roles in endothelial cell function, inflammation, and fibrogenesis ( 8 9 10 11 ).…”

Chagas Disease in People with HIV: A Narrative Review

“…Chronic Chagas disease, cardiac and gastrointestinal manifestations: Whether PWH are more susceptible to cardiomyopathy when co-infected with T. cruzi remains unclear [ 26 ]. One Brazilian group investigated potential associations between T. cruzi parasitemia and the impact of HIV infection on cardiomyopathy [ 36 ]. Their data suggest that HIV infection may protect against the development and progression of cardiopathy, potentially due to a synergistic effect of HIV and/or ART or reduced cellular immunity attenuating a type-1 helper T-cell-mediated response in the myocardium.…”

“…It is more common in PWH with low CD4 cell counts [ 44 ] (particularly less than 100 cells/mm 3 ) and is considered to be an opportunistic infection in people with AIDS. IL-18 serum concentrations may influence or predict the risk of T. cruzi reactivation in PWH [ 36 ].…”

Trypanosoma cruzi genetic diversity: impact on transmission cycles and Chagas disease

“… 62 On the other hand, the protective role of IL17A AA, IL18 AA, and IL1B TC genotypes against development/progression of cardiomyopathy has been reported. 63 …”