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A DNA vaccine encoding CCL4/MIP-1beta enhances myocarditis in experimental Trypanosoma cruzi infection in rats
Ester Roffê1, Adriano L S Souza, Bráulia C Caetano
1Departamento 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.
Insights
The study investigated the role of CCL4/MIP-1beta in Chagas disease myocarditis. Results indicate that this chemokine may exacerbate inflammation and fibrosis, rather than control parasite replication in infected rats.
Area of Science:
- Immunology
- Parasitology
- Cardiovascular Research
Background:
- Chagas' disease, caused by Trypanosoma cruzi, leads to significant cardiovascular issues in Latin America.
- Inflammation in chronic Chagas disease is disproportionate to parasite load, suggesting complex immune involvement.
- Chemokines and their receptors are implicated in Chagas disease inflammation, but their specific roles remain unclear.
Purpose of the Study:
- To evaluate the impact of a DNA vaccine encoding CCL4/MIP-1beta on Trypanosoma cruzi-induced myocarditis in rats.
- To understand the role of CCL4/MIP-1beta in the inflammatory and pathological processes of Chagas disease.
Main Methods:
- Holtzman rats were immunized with a CCL4/MIP-1beta DNA vaccine prior to infection with a T. cruzi clone.
- Parasitemia, myocardial inflammation, and fibrosis were assessed at various time points post-infection.
- Expression levels of CCL2/MCP-1 and CCL4/MIP-1beta were correlated with inflammatory kinetics.
Main Results:
- The CCL4/MIP-1beta DNA vaccine increased anti-CCL4/MIP-1beta levels in infected rats.
- Vaccination led to exacerbated myocardial inflammation and fibrosis.
- No significant alterations in parasitemia or myocardial parasitism were observed due to the vaccine.
Conclusions:
- CCL4/MIP-1beta appears to play a role in preventing excessive inflammation and pathology in Chagas disease.
- This chemokine may not be directly involved in controlling Trypanosoma cruzi replication.
- Targeting CCL4/MIP-1beta warrants further investigation for therapeutic strategies in Chagas disease.
Abstract:
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.
