Detecting imperative genes and infiltrating immune cells in chronic Chagas cardiomyopathy by bioinformatics analysis.

Abstract

Chronic Chagas cardiomyopathy (CCC) is an acquired inflammatory cardiomyopathy triggered by the protozoan Trypanosoma cruzi infection. Although microvascular and neurogenic dysfunction and inflammation with persistent parasite presence in the heart may play a major pathogenetic role, little is known about the overall picture of gene co-expression regulating CCC. In this study, we aimed to explore the key biological pathways, hub genes and the landscope of infiltrating immune cells associated with inflammation in chronic Chagas cardiomyopathy. A weighted gene co-expression network analysis (WGCNA) was conducted based on the gene expression profiles from patients with and without chronic Chagas cardiomyopathy (GSE84796). Twelve coexpression modules were identified from the top 25% variant genes. Among them, the turquoise and black module were significantly positively correlated with CCC, which were highly enriched in Th1 and Th2 cell differentiation, the Cytokine-cytokine receptor interaction,NF-kappa B signaling pathway and T cell receptor signaling pathway. In addition, four genes (TBX21, ZAP70,IL2RB and CD69) were selected as candidate hub genes. Gene expression for hub genes were higher in CCC tissues compared to tissues from healthy controls. Additionally, gene set enrichment analysis (GSEA) analysis showed that high expressions of these hub genes were significantly correlated with interferon α response and interferon γ response. The microarray dataset GSE41089 further confirmed that although CD69 was not detected, the expression of TBX21, IL2RB and ZAP70 was also significantly up-regulated in the CCC mice compared to controls. We further studied the immune cells infiltration in CCC patients with CIBERSORT. The fraction of Mast cells activated,T cells CD8 and T cells gamma delta were significantly increased in CCC patients compared with control. Our research provides a more effective understanding of the pathogenesis of CCC and could help in future strategies for new diagnostic and therapeutic approaches for CCC patients.