title: Role of CCL3/MIP-1alpha and CCL5/RANTES during acute Trypanosoma cruzi infection in rats.
abstract: Chagas' disease is caused by Trypanosoma cruzi infection and is characterized by chronic fibrogenic inflammation and heart dysfunction. Chemokines are produced during infection and drive tissue inflammation. In rats, acute infection is characterized by intense myocarditis and regression of inflammation after control of parasitism. We investigated the role of CCL3 and CCL5 during infection by using DNA vaccination encoding for each chemokine separately or simultaneously. MetRANTES treatment was used to evaluate the role of CCR1 and CCR5, the receptors for CCL3 and CCL5. Vaccination with CCL3 or CCL5 increased heart parasitism and decreased local IFN-gamma production, but did not influence intensity of inflammation. Simultaneous treatment with both plasmids or treatment with MetRANTES enhanced cardiac inflammation, fibrosis and parasitism. In conclusion, chemokines CCL3 and CCL5 are relevant, but not essential, for control of T. cruzi infection in rats. On the other hand, combined blockade of these chemokines or their receptors enhanced tissue inflammation and fibrosis, clearly contrasting with available data in murine models of T. cruzi infection. These data reinforce the important role of chemokines during T. cruzi infection but suggest that caution must be taken when expanding the therapeutic modulation of the chemokine system in mice to the human infection.
authors.affiliation: Departamento de Bioquímica e Imunologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil. roffeest@niaid.nih.gov
authors.forename: Ester
authors.initials: E
authors.lastname: Roffê
authors.forename: Fabiano
authors.initials: F
authors.lastname: Oliveira
authors.forename: Adriano L S
authors.initials: AL
authors.lastname: Souza
authors.forename: Vanessa
authors.initials: V
authors.lastname: Pinho
authors.forename: Danielle G
authors.initials: DG
authors.lastname: Souza
authors.forename: Patrícia R S
authors.initials: PR
authors.lastname: Souza
authors.forename: Remo C
authors.initials: RC
authors.lastname: Russo
authors.forename: Helton C
authors.initials: HC
authors.lastname: Santiago
authors.forename: Alvaro J
authors.initials: AJ
authors.lastname: Romanha
authors.forename: Herbert B
authors.initials: HB
authors.lastname: Tanowitz
authors.forename: Jesus G
authors.initials: JG
authors.lastname: Valenzuela
authors.forename: Mauro M
authors.initials: MM
authors.lastname: Teixeira
mesh_terms: D000818:Animals; D002598:Chagas Cardiomyopathy / Q000276:immunology* / Q000473:pathology; D054405:Chemokine CCL3 / Q000276:immunology*; D018946:Chemokine CCL5 / Q000276:immunology*; D006321:Heart / Q000469:parasitology; D009206:Myocardium / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D014349:Trypanosoma cruzi / Q000276:immunology* / Q000472:pathogenicity; D019444:Vaccines, DNA / Q000008:administration & dosage
chemical_list: D054405:Chemokine CCL3; D018946:Chemokine CCL5; D019444:Vaccines, DNA
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