Article ; Online: Aspirin-triggered resolvin D1 reduces parasitic cardiac load by decreasing inflammation in a murine model of early chronic Chagas disease.
PLoS neglected tropical diseases
2021 Volume 15, Issue 11, Page(s) e0009978
Abstract: Background: Chagas disease, caused by the protozoan Trypanosoma cruzi, is endemic in Latin America and is widely distributed worldwide because of migration. In 30% of cases, after years of infection and in the absence of treatment, the disease ... ...
| Abstract | Background: Chagas disease, caused by the protozoan Trypanosoma cruzi, is endemic in Latin America and is widely distributed worldwide because of migration. In 30% of cases, after years of infection and in the absence of treatment, the disease progresses from an acute asymptomatic phase to a chronic inflammatory cardiomyopathy, leading to heart failure and death. An inadequate balance in the inflammatory response is involved in the progression of chronic Chagas cardiomyopathy. Current therapeutic strategies cannot prevent or reverse the heart damage caused by the parasite. Aspirin-triggered resolvin D1 (AT-RvD1) is a pro-resolving mediator of inflammation that acts through N-formyl peptide receptor 2 (FPR2). AT-RvD1 participates in the modification of cytokine production, inhibition of leukocyte recruitment and efferocytosis, macrophage switching to a nonphlogistic phenotype, and the promotion of healing, thus restoring organ function. In the present study, AT-RvD1 is proposed as a potential therapeutic agent to regulate the pro-inflammatory state during the early chronic phase of Chagas disease. Methodology/principal findings: C57BL/6 wild-type and FPR2 knock-out mice chronically infected with T. cruzi were treated for 20 days with 5 μg/kg/day AT-RvD1, 30 mg/kg/day benznidazole, or the combination of 5 μg/kg/day AT-RvD1 and 5 mg/kg/day benznidazole. At the end of treatment, changes in immune response, cardiac tissue damage, and parasite load were evaluated. The administration of AT-RvD1 in the early chronic phase of T. cruzi infection regulated the inflammatory response both at the systemic level and in the cardiac tissue, and it reduced cellular infiltrates, cardiomyocyte hypertrophy, fibrosis, and the parasite load in the heart tissue. Conclusions/significance: AT-RvD1 was shown to be an attractive therapeutic due to its regulatory effect on the inflammatory response at the cardiac level and its ability to reduce the parasite load during early chronic T. cruzi infection, thereby preventing the chronic cardiac damage induced by the parasite. |
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| MeSH term(s) | Animals ; Chagas Cardiomyopathy/drug therapy ; Chagas Cardiomyopathy/genetics ; Chagas Cardiomyopathy/immunology ; Chagas Cardiomyopathy/parasitology ; Chronic Disease/drug therapy ; Disease Models, Animal ; Docosahexaenoic Acids/administration & dosage ; Female ; Heart/drug effects ; Humans ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Myocardium/immunology ; Nitroimidazoles/administration & dosage ; Parasite Load ; Receptors, Formyl Peptide/genetics ; Receptors, Formyl Peptide/immunology ; Trypanosoma cruzi/physiology |
| Chemical Substances | Nitroimidazoles ; Receptors, Formyl Peptide ; formyl peptide receptor 2, mouse ; resolvin D1 ; Docosahexaenoic Acids (25167-62-8) ; benzonidazole (YC42NRJ1ZD) |
| Language | English |
| Publishing date | 2021-11-16 |
| Publishing country | United States |
| Document type | Journal Article ; Research Support, Non-U.S. Gov't |
| ZDB-ID | 2429704-5 |
| ISSN | 1935-2735 ; 1935-2727 |
| ISSN (online) | 1935-2735 |
| ISSN | 1935-2727 |
| DOI | 10.1371/journal.pntd.0009978 |
| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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