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Published on: November 5, 2021
Resolvin D1 Administration Is Beneficial in Trypanosoma cruzi Infection
Aline L Horta1,2, Tere Williams1, Bing Han1
1Division of Parasitology, Department of Pathology, Albert Einstein College of Medicine, New York, New York, USA.
Insights
Resolvin D1 (RvD1) therapy improved survival and reduced parasite load in acute Chagas disease. It also decreased cardiac fibrosis and inflammation in chronic Chagas disease models.
Area of Science:
- Parasitology
- Immunology
- Pharmacology
Background:
- Chagas disease, caused by *Trypanosoma cruzi*, affects millions globally, leading to chronic inflammation and cardiomyopathy.
- Current treatments for *T. cruzi* infection lack efficacy in altering disease outcomes.
- Resolvin D1 (RvD1), a proresolving lipid mediator, shows potential in managing inflammatory conditions.
Purpose of the Study:
- To investigate the therapeutic potential of exogenous RvD1 in a murine model of Chagas disease.
- To evaluate RvD1's effects on both acute and chronic *T. cruzi* infection.
- To assess RvD1's impact on parasite replication, inflammatory markers, and cardiac pathology.
Main Methods:
- CD-1 mice infected with *T. cruzi* were treated with RvD1 during acute (days 5, 10, 15) or chronic (days 60, 65, 70) infection phases.
- Survival rates, parasite replication, and levels of cytokines (interferon-gamma, TGF-β, interleukin-10) were measured.
- Cardiac tissue analysis included assessment of collagen content to evaluate fibrosis.
Main Results:
- RvD1 therapy significantly increased survival and controlled parasite replication in acute *T. cruzi* infection.
- In chronic infection, RvD1 reduced levels of interferon-gamma and transforming growth factor-β (TGF-β).
- RvD1 treatment led to increased interleukin-10 levels and decreased cardiac collagen content, indicating reduced fibrosis.
Conclusions:
- Exogenous RvD1 demonstrates significant therapeutic benefits in a murine model of Chagas disease.
- RvD1 therapy effectively dampens inflammatory responses and promotes resolution of *T. cruzi* infection.
- RvD1 holds promise for preventing cardiac fibrosis and improving outcomes in Chagas disease patients.
Abstract:
Chagas disease is a major public health issue, affecting ∼10 million people worldwide. Transmitted by a protozoan named Trypanosoma cruzi, this infection triggers a chronic inflammatory process that can lead to cardiomyopathy (Chagas disease). Resolvin D1 (RvD1) is a novel proresolution lipid mediator whose effects on inflammatory diseases dampens pathological inflammatory responses and can restore tissue homeostasis. Current therapies are not effective in altering the outcome of T. cruzi infection, and as RvD1 has been evaluated as a therapeutic agent in various inflammatory diseases, we examined if exogenous RvD1 could modulate the pathogenesis of Chagas disease in a murine model. CD-1 mice infected with the T. cruzi Brazil strain were treated with RvD1. Mice were administered 3 μg/kg of body weight RvD1 intraperitoneally on days 5, 10, and 15 to examine the effect of RvD1 on acute disease or administered the same dose on days 60, 65, and 70 to examine its effects on chronic infection. RvD1 therapy increased the survival rate and controlled parasite replication in mice with acute infection and reduced the levels of interferon gamma and transforming growth factor β (TGF-β) in mice with chronic infection. In addition, there was an increase in interleukin-10 levels with RvD1 therapy in both mice with acute infection and mice with chronic infection and a decrease in TGF-β levels and collagen content in cardiac tissue. Together, these data indicate that RvD1 therapy can dampen the inflammatory response, promote the resolution of T. cruzi infection, and prevent cardiac fibrosis.
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