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Type 1 chemokine receptor expression in Chagas' disease correlates with morbidity in cardiac patients

Juliana A S Gomes1, Lilian M G Bahia-Oliveira, Manoel Otávio C Rocha

  • 1Laboratório de Imunologia Celular e Molecular-Centro de Pesquisas René Rachou/FIOCRUZ, Av. Augusto de Lima 1715, 30190-002, Belo Horizonte, MG, Brazil.

Infection and Immunity
|November 22, 2005
PubMed

Insights

Chagas

Area of Science:

  • Immunology and Infectious Diseases
  • Molecular and Cellular Biology

Background:

  • Chemokines and chemokine receptors (CKRs) regulate leukocyte migration during inflammation.
  • CKRs are key immunological markers for type 1 (e.g., CCR5, CXCR3) and type 2 (e.g., CCR3, CCR4) immune responses.
  • Chagas' disease presents indeterminate (IND) and cardiac (CARD) clinical forms, differing in immune responses.

Purpose of the Study:

  • To evaluate the coexpression of CKRs and intracellular cytokines on T cells in Chagas' disease patients.
  • To investigate immune response differences between IND and CARD clinical forms of Chagas' disease.
  • To correlate CKR and cytokine expression with cardiac pathology development in Chagas' disease.

Main Methods:

  • Peripheral blood T CD4+ and CD8+ cells from IND and CARD individuals were analyzed.
  • Cells were stimulated in vitro with Trypanosoma cruzi antigens.
  • Coexpression of specific CKRs (CCR2, CCR3, CCR5, CXCR3, CXCR4) and cytokines (IL-10, IL-4, TNF-alpha, IFN-gamma) was measured.

Main Results:

  • CARD individuals showed higher coexpression of CCR5/IFN-gamma, CXCR3/IFN-gamma, and CXCR3/TNF-alpha on T cells compared to IND individuals.
  • CARD individuals exhibited lower coexpression of CCR3/IL-10 and CCR3/IL-4 on T cells compared to IND individuals.
  • Positive correlations between CCR5/CXCR3 and IFN-gamma were found in CARD patients; CCR3 and IL-4/IL-10 correlations were observed in IND patients.

Conclusions:

  • A type 1 immune response, marked by specific CKR and cytokine profiles, is exacerbated in cardiac Chagas' disease patients.
  • This exacerbated type 1 immune response is associated with the development of heart pathology in Chagas' disease.
  • CKR and cytokine profiling can serve as immunological markers for Chagas' disease progression and severity.

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