ArticlePLoS neglected tropical diseases2012
Myocardial chemokine expression and intensity of myocarditis in Chagas cardiomyopathy are controlled by polymorphisms in CXCL9 and CXCL10.
Article in PLoS neglected tropical diseases, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 69 papers, 1 of them a synthesis that pooled it.
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Who cites it
69 citing papers in PubMed, 1 synthesis or guideline pooled it, 119 citations in OpenAlex.
- SBC Guideline on the Diagnosis and Treatment of Patients with Cardiomyopathy of Chagas Disease - 2023.Arquivos brasileiros de cardiologia · 2023Guideline
- Effects of MK-886, an inhibitor of the 5-lipoxygenase-activating protein, on peripheral blood mononuclear cells from patients with Chagas' heart disease.Revista da Sociedade Brasileira de Medicina Tropical · 2026Article
- Single-Cell Targeted Transcriptomics Reveals Subset-Specific Immune Signatures Differentiating Asymptomatic and Cardiac Patients With Chronic Chagas Disease.The Journal of infectious diseases · 2025Article
- Sex Differences in Chagas Cardiomyopathy: a Comprehensive Review.Current heart failure reports · 2025Review
- The causal relationship between circulating inflammatory proteins and heart failure: A two-sample Mendelian randomization study.Medicine · 2025Article
- Higher T-bet and IFN-γ expression in advanced chagasic megaesophagus indicates Th1 response in the chronic phase.Revista do Instituto de Medicina Tropical de Sao Paulo · 2025Article
- Cardiac and Digestive Forms of Chagas Disease: An Update on Pathogenesis, Genetics, and Therapeutic Targets.Mediators of inflammation · 2025Review
- Role of the CX3CL1/CX3CR1 axis in iron metabolism and immune regulation during acuteFrontiers in immunology · 2025Article
- Self and parasite-derived peptides selected upon DERAA-bearing HLA-DRB1 alleles activate CD4+ T cells from Chagas cardiomyopathy patients and are associated with ventricular dysfunction.Frontiers in immunology · 2025Article
- Cardiac involvement in Chagas disease and African trypanosomiasis.Nature reviews. Cardiology · 2024Review
- The Functions of Cytokines in the Cardiac Immunopathogenesis of Chagas Disease.Pathogens (Basel, Switzerland) · 2024Review
- Case report of fatal immune-mediated myocarditis following treatment with davoceticept (ALPN-202), a PD-L1-dependent CD28 costimulator and dual PD-L1/CTLA-4 checkpoint inhibitor, in combination with pembrolizumab.Journal for immunotherapy of cancer · 2024Article
- Exercise Training Reduces Inflammation and Fibrosis and Preserves Myocardial Function and Perfusion in a Model of Chronic Chagas Cardiomyopathy.Arquivos brasileiros de cardiologia · 2024Article
- Correlation of blood-based immune molecules with cardiac gene expression profiles reveals insights into Chagas cardiomyopathy pathogenesis.Frontiers in immunology · 2024Article
- Parasite DNA and Markers of Decreased Immune Activation Associate Prospectively with Cardiac Functional Decline over 10 Years amongInternational journal of molecular sciences · 2023Article
- Inflammation and mitochondria in the pathogenesis of chronic Chagas disease cardiomyopathy.Experimental biology and medicine (Maywood, N.J.) · 2023Review
- Narrowing the Relationship between Human CCR5 Gene Polymorphisms and Chagas Disease: Systematic Review and Meta-Analysis.Life (Basel, Switzerland) · 2023Article
- Article
- Integrated bioinformatics analysis for identifying key genes and pathways in female and male patients with dilated cardiomyopathy.Scientific reports · 2023Article
- Blocking activation of CD4Clinical immunology (Orlando, Fla.) · 2023Article
9 more citing papers are in PubMed but not listed here.
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Authors and funding
20 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundChronic Chagas cardiomyopathy (CCC), a life-threatening inflammatory dilated cardiomyopathy, affects 30% of the approximately 8 million patients infected by Trypanosoma cruzi. Even though the Th1 T cell-rich myocarditis plays a pivotal role in CCC pathogenesis, little is known about the factors controlling inflammatory cell migration to CCC myocardium. METHODS AND
resultsUsing confocal immunofluorescence and quantitative PCR, we studied cell surface staining and gene expression of the CXCR3, CCR4, CCR5, CCR7, CCR8 receptors and their chemokine ligands in myocardial samples from end-stage CCC patients. CCR5+, CXCR3+, CCR4+, CCL5+ and CXCL9+ mononuclear cells were observed in CCC myocardium. mRNA expression of the chemokines CCL5, CXCL9, CXCL10, CCL17, CCL19 and their receptors was upregulated in CCC myocardium. CXCL9 mRNA expression directly correlated with the intensity of myocarditis, as well as with mRNA expression of CXCR3, CCR4, CCR5, CCR7, CCR8 and their ligands. We also analyzed single-nucleotide polymorphisms for genes encoding the most highly expressed chemokines and receptors in a cohort of Chagas disease patients. CCC patients with ventricular dysfunction displayed reduced genotypic frequencies of CXCL9 rs10336 CC, CXCL10 rs3921 GG, and increased CCR5 rs1799988CC as compared to those without dysfunction. Significantly, myocardial samples from CCC patients carrying the CXCL9/CXCL10 genotypes associated to a lower risk displayed a 2-6 fold reduction in mRNA expression of CXCL9, CXCL10, and other chemokines and receptors, along with reduced intensity of myocarditis, as compared to those with other CXCL9/CXCL10 genotypes.
conclusionsResults may indicate that genotypes associated to reduced risk in closely linked CXCL9 and CXCL10 genes may modulate local expression of the chemokines themselves, and simultaneously affect myocardial expression of other key chemokines as well as intensity of myocarditis. Taken together our results may suggest that CXCL9 and CXCL10 are master regulators of myocardial inflammatory cell migration, perhaps affecting clinical progression to the life-threatening form of CCC.
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