Differential expression profile of genes involved in the immune response associated to progression of chronic Chagas disease

• Published in: PLoS neglected tropical diseases Vol. 17; no. 7; p. e0011474
• Main Authors: Gómez, Inmaculada, López, Manuel Carlos, Egui, Adriana, Palacios, Génesis, Carrilero, Bartolomé, Benítez, Celia, Simón, Marina, Segovia, Manuel, Carmelo, Emma, Thomas, M Carmen
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 01.07.2023
• Subjects: Analysis; Antigens; Asymptomatic; Biology and Life Sciences; Biomarkers; Cardiomyopathy; Cell activation; Chagas Cardiomyopathy - genetics; Chagas disease; Chagas Disease - parasitology; Chemokines; Chronic Disease; Chronic illnesses; Cluster analysis; Cohorts; Coronary artery disease; Cytokines; Cytokines - metabolism; Defence mechanisms; Development and progression; DNA testing; Down-regulation; Electrocardiography; Gene expression; Gene set enrichment analysis; Genes; Genetic aspects; Genomics; Heart; Heart diseases; Heterogeneity; Humans; Immune response; Immune system; Immunity; Immunology; Infections; Inflammation; Inflammatory response; Interleukin 10; Interleukin 12; Leukocytes, Mononuclear; Lymphocyte Activation; Medicine and Health Sciences; Nitrogen dioxide; Nucleotide sequence; Parasites; PCR; Peripheral blood mononuclear cells; Physical Sciences; Principal components analysis; Protozoa; Research and Analysis Methods; Tropical diseases; Trypanosoma cruzi - genetics; Vector-borne diseases; Spain
• ISSN: 1935-2735; 1935-2727; 1935-2735
• DOI: 10.1371/journal.pntd.0011474

Patients with chronic Chagas disease present marked clinical and immunological heterogeneity. During the disease, multiple immune mechanisms are activated to fight the parasite. The purpose of this study was to investigate the expression patterns of genes involved in relevant immunological processes throughout the disease in patients with chronic Chagas disease. High-throughput RT-qPCR with QuantStudio 12K Flex real-time PCR system was used to evaluate the expression of 106 immune-related genes in PBMC from a cohort of cardiac Chagas disease patients (CCC I), asymptomatic patients (IND) and healthy donors (HD) after being stimulated with T. cruzi soluble antigens. Principal component analysis (PCA), cluster analysis and volcano plots were used to identify differentially expressed genes. In addition, gene set enrichment analysis (GSEA) was employed to identify the enriched immunological pathways in which these genes are involved. PCA revealed the existence of a statistically divergent expression profile of the 36 genes correlated with PC1 between CCC I patients and HD (p < 0.0001). Differential gene expression analysis revealed upregulation of 41 genes (expression fold-change > 1.5) and downregulation of 14 genes (expression fold-change < 0.66) (p = 8.4x10-13 to p = 0.007) in CCC I patients versus HD. Furthermore, significant differences in the expression level of specific genes have been identified between CCC I and IND patients (8 up and 1 downregulated). GSEA showed that several upregulated genes in CCC I patients participate in immunological pathways such as antigen-dependent B cell activation, stress induction of HSP regulation, NO2-dependent IL12 pathway in NK cells, cytokines-inflammatory response and IL-10 anti-inflammatory signaling. Cardiac Chagas disease patients show an antigen-specific differential gene expression profile in which several relevant immunological pathways seem to be activated. Assessment of gene expression profiles reveal unique insights into the immune response that occurs along chronic Chagas disease.