Treatment of chronically Trypanosoma cruzi-infected mice with a CCR1/CCR5 antagonist (Met-RANTES) results in amelioration of cardiac tissue damage.
Microbes Infect
; 11(2): 264-73, 2009 Feb.
Article
em En
| MEDLINE
| ID: mdl-19100857
ABSTRACT
The comprehension of the molecular mechanisms leading to Trypanosoma cruzi-elicited heart dysfunction might contribute to design novel therapeutic strategies aiming to ameliorate chronic Chagas disease cardiomyopathy. In C3H/He mice infected with the low virulence T. cruzi Colombian strain, the persistent cardiac inflammation composed mainly of CCR5(+) T lymphocytes parallels the expression of CC-chemokines in a pro-inflammatory IFN-gamma and TNF-alpha milieu. The chronic myocarditis is accompanied by increased frequency of peripheral CCR5(+)LFA-1(+) T lymphocytes. The treatment of chronically T. cruzi-infected mice with Met-RANTES, a selective CCR1/CCR5 antagonist, led to a 20-30% decrease in CD4(+) cell numbers as well as IL-10, IL-13 and TNF-alpha expression. Further, Met-RANTES administration impaired the re-compartmentalization of the activated CD4(+)CCR5(+) lymphocytes. Importantly, Met-RANTES treatment resulted in significant reduction in parasite load and fibronectin deposition in the heart tissue. Moreover, Met-RANTES treatment significantly protected T. cruzi-infected mice against connexin 43 loss in heart tissue and CK-MB level enhancement, markers of heart dysfunction. Thus, our results corroborate that therapeutic strategies based on the modulation of CCR1/CCR5-mediated cell migration and/or effector function may contribute to cardiac tissue damage limitation during chronic Chagas disease.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Trypanosoma cruzi
/
Doença de Chagas
/
Quimiocina CCL5
/
Receptores CCR1
/
Antagonistas dos Receptores CCR5
/
Fatores Imunológicos
/
Miocárdio
Limite:
Animals
Idioma:
En
Ano de publicação:
2009
Tipo de documento:
Article