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Chemokine receptor expression on the surface of peripheral blood mononuclear cells in Chagas disease
Andre Talvani1, Manoel O C Rocha, Antonio L Ribeiro
1Departamento de Bioquímica e Imunologia, Instituto de Ciências Biológicas, Belo Horizonte, Minas Gerais, Brazil.
Insights
Chemokine receptor CCR5 and CXCR4 expression on immune cells differs in chronic Chagasic cardiomyopathy (CCC). Mild CCC shows higher CCR5, severe CCC shows lower CXCR4, correlating with heart function decline.
Area of Science:
- Immunology
- Cardiology
- Infectious Diseases
Background:
- Chagasic cardiomyopathy (CCC) is a severe complication of Trypanosoma cruzi infection.
- The role of chemokine receptors in the pathogenesis of CCC is not fully understood.
- Immune cell dysregulation is implicated in the progression of heart damage.
Purpose of the Study:
- To investigate the expression patterns of chemokine receptors (CCR1, CCR2, CCR5, CXCR4) on peripheral blood mononuclear cells (PBMCs) in patients with CCC.
- To determine if chemokine receptor expression correlates with the severity of cardiac dysfunction in CCC.
Main Methods:
- Peripheral blood mononuclear cells were isolated from patients with chronic Chagasic Cardiomyopathy (CCC) and noninfected individuals.
- Flow cytometry was used to evaluate the surface expression of chemokine receptors CCR1, CCR2, CCR5, and CXCR4 on CD4+, CD8+, and CD14+ cell subsets.
- Expression levels were compared between different CCC severity groups and healthy controls.
Main Results:
- CCR5 and CXCR4 expression differed significantly on CD4+, CD8+, and CD14+ cell subsets between CCC patients and noninfected individuals.
- Patients with mild CCC exhibited elevated leukocyte CCR5 expression compared to noninfected individuals and those with severe CCC.
- Leukocyte CXCR4 expression was reduced in patients with severe CCC.
- Differential expression of CCR5 and CXCR4 correlated inversely with cardiac function, with lower expression linked to poorer heart function.
Conclusions:
- The chemokine system, particularly CCR5 and CXCR4, may play a role in the early stages of Chagasic Cardiomyopathy.
- Heart failure-induced cardiac remodeling in CCC influences immune cell parameters, affecting chemokine receptor expression.
- These findings suggest potential therapeutic targets within the chemokine system for managing CCC progression.
Abstract:
We evaluated the expression of chemokine receptors (CCR1, CCR2, CCR5, and CXCR4) on the surface of peripheral blood mononuclear cells obtained from patients with chronic chagasic cardiomyopathy (CCC) and noninfected individuals. Only CCR5 and CXCR4 expression was different on the surface of the subsets (CD4, CD8, and CD14) evaluated. Patients with mild CCC had elevated leukocyte expression of CCR5, compared with noninfected individuals or those with severe disease. CXCR4 expression was lower on leukocytes from patients with severe CCC. The differential expression of both receptors on leukocytes of patients with CCC was consistent and clearly correlated with the degree of heart function such that the lower the heart function, the lower the expression of either CCR5 or CXCR4. These results highlight the possible participation of the chemokine system in early forms of chagasic cardiomyopathy and the relevance of heart failure-induced remodeling in modifying immune parameters in infected individuals.
