A DNA vaccine encoding CCL4/MIP-1beta enhances myocarditis in experimental Trypanosoma cruzi infection in rats.
Chagas' disease, caused by Trypanosoma cruzi, is a major cause of cardiovascular disease in Latin America. Exacerbated inflammation disproportional to parasite load characterizes chronic myocardial lesions in chagasic patients. Chemokines and their receptors are expected to account for the renewed inflammatory processes after the inoculation of the parasite, but their potential unique functions are far from being clear. Herein, we evaluated the effect of a DNA vaccine encoding CCL4/MIP-1beta, a CC-chemokine, in T. cruzi-elicited myocarditis in rats. Holtzman rats were given intramuscularly cardiotoxin and the CCL4/MIP-1beta DNA-containing plasmid (100microg) was delivered in this muscular site four times. Fourteen days after last immunization, animals were inoculated with a myotropical CL-Brener T. cruzi clone. Peak of parasitism was observed at day 15 after infection, preceding the peak of myocardial inflammation at day 20. Myocarditis was still intense at day 30, but the inflammatory infiltrates showed a more focal distribution. The expression of CCL2/MCP-1 and CCL4/MIP-1beta correlated closely with the kinetics of myocardial inflammation. The CCL4/MIP-1beta DNA vaccine induced an increase of the levels of the anti-CCL4/MIP-1beta observed in T. cruzi-infected animals. This was associated with an exacerbation of myocardial inflammation and fibrosis, although alterations in parasitemia and myocardial parasitism were not observed. Our data suggest that CCL4/MIP-1beta plays a role in preventing excessive inflammation and pathology rather than in controlling parasite replication.
Roffê
Ester
E
Departamento de Bioquímica e Imunologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Avenida Antonio Carlos 6627, Pampulha, Belo Horizonte, Minas Gerais 31270-901, Brazil.
Souza
Adriano L S
AL
Caetano
Bráulia C
BC
Machado
Patrícia P
PP
Barcelos
Lucíola S
LS
Russo
Remo C
RC
Santiago
Helton C
HC
Souza
Danielle G
DG
Pinho
Vanessa
V
Tanowitz
Herbert B
HB
Camargos
Elisabeth R S
ER
Bruña-Romero
Oscar
O
Teixeira
Mauro M
MM
D000818:Animals; D002598:Chagas Cardiomyopathy / Q000276:immunology / Q000473:pathology*; D054407:Chemokine CCL4; D019742:Chemokines, CC / Q000235:genetics / Q000276:immunology*; D004195:Disease Models, Animal; D005786:Gene Expression Regulation; D006321:Heart / Q000469:parasitology; D006651:Histocytochemistry; D009206:Myocardium / Q000473:pathology; D018512:Parasitemia; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D014349:Trypanosoma cruzi / Q000276:immunology* / Q000302:isolation & purification; D019444:Vaccines, DNA / Q000235:genetics / Q000276:immunology*
C066507:CCL4 protein, human; D054407:Chemokine CCL4; D019742:Chemokines, CC; D012333:RNA, Messenger; D019444:Vaccines, DNA