Herein, we showed that the function and expression of the IL-27 receptor and the gene expression of transcription factors involved in IL-27 signaling pathways were altered in T. cruzi-infected subjects presenting cardiac disease, and CD4+ T-cell responses to T. cruzi were improved upon the exogenous addition of IL-27 and IL-7 only in the face of functional IL-27/IL-27R and IL-7/IL-7R pathways. The gene discussed is IL27RA; the disease is heart disorder.