Alterations in the IL27 pathway are correlated with the loss of Trypanosoma cruzispecific T cells in patients with chronic Chagas disease

AILEN NATALE; MINNING T; ALVAREZ M; R. J. VIOTTI; BERTOCCHI GL; LOCCOCO B; ALBAREDA M C; TARLETON RL; LAUCELLA SA

Congreso; 66th Annual Meeting ASTMH; 2017

We have previously shown that chronically T. cruzi-infected subjects bear several features of a process of immune exhaustion including an inverse correlation between disease severity and the magnitude of T cell responses, and alterations in the signaling pathway of the IL-7R. Like IL-7, IL-27 also exerts its function through STAT5. In this study, we performed an analysis of the expression of the IL-27R components (CD130 and WSX1 chains) on CD4+ and CD8+ T cells, and evaluated IL-27-dependent signaling events in relation to T cell responses in patients at different clinical stage of chronic Chagas disease using polychromatic flow cytometry. Subjects with no signs of cardiac disease showed a decrease in CD130+WSX1+CD4+ T cells and an increase in CD130+WSX1+CD8+ T cells compared with either patients exhibiting heart disease or uninfected controls. T. cruzi infection in vitro, was able to stimulate the downregulation of the IL-27R on CD4+ T cells and the upregulation on CD8+ T cells. IL-27-induced phosphorylation of STAT1, STAT3 and STAT5 was lower in patients with heart disease compared with asymptomatic patients and inversely associated with the frequency of T. cruzi-specific IFN-gamma-producing T cells measured by ELISPOT assay. STAT5- downstream gene expression of tbx21, eomes, gzmb and cxcl9 assessed by q-RTPCR was also reduced in patients with cardiomyopathy. These findings support a possible role of the IL-27R signaling pathway in promoting T. cruzi-specific T cells responses.