Clinical and experimental immunology 2017 05 24() doi 10.1111/cei.12992
Cardiomyopathy is the most severe outcome of Chagas disease, causing over 12,000 deaths/year. Immune cells participate in cardiomyopathy development either by direct tissue destruction, or by driving inflammation. We have shown that CD4-CD8- (double negative – DN) T cells are major sources of inflammatory and anti-inflammatory cytokines, associated with the cardiac (CARD) and indeterminate (IND) forms of Chagas disease, respectively. Here, we sought to identify Trypanosoma cruzi derived components that lead to activation of DN T cells in Chagas patients. Glycolipid (GCL), lipid (LIP) and protein-enriched (PRO) fractions derived from trypomastigote forms of T. cruzi were utilized to stimulate cells from IND and CARD patients to determine DN T cell activation by evaluating CD69 and cytokine expression. We observed that GCL, but not LIP or PRO fractions, induced higher activation of DN T cells, especially TCR-γδ DN T, from IND and CARD. GCL led to an increase in TNF and IL-10 expression by TCR-γδ DN T cells from IND, while inducing IFN-γ expression by TCR-γδ DN T cells from CARD. This lead to an increase in the ratio IFN-γ/IL-10 in TCR-γδ DN T cells from CARD, favoring an inflammatory profile. These results identify GCL as the major T. cruzi component responsible for activation of DN T cells in chronic Chagas disease, predominantly associated with an inflammatory profile in CARD but not IND. These findings may have implications for designing new strategies of control or prevention of Chagas disease cardiomyopathy by modulating the response to GCL. This article is protected by copyright. All rights reserved.