Resolvin D1 Administration Is Beneficial in Trypanosoma cruzi Infection.

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 ß (TGF-ß) 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-ß 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.

Expression and production of cardiac angiogenic mediators depend on the Trypanosoma cruzi-genetic population in experimental C57BL/6 mice infection.

Mammalian cardiac cells are important targets to the protozoan Trypanosoma cruzi. The inflammatory reaction in the host aims at eliminating this parasite, can lead to cell destruction, fibrosis and hypoxia. Local hypoxia is well-defined stimulus to the production of angiogenesis mediators. Assuming that different genetic T. cruzi populations induce distinct inflammation and disease patterns, the current study aims to investigate whether the production of inflammatory and angiogenic mediators is a parasite strain-dependent condition. C57BL/6 mice were infected with the Y and Colombian strains of T. cruzi and euthanized at the 12th and 32nd days, respectively. The blood and heart tissue were processed in immune assays and/or qPCR (TNF, IL-17, IL-10, CCL2, CCL3, CCL5, CCR2, CCR5 and angiogenic factors VEGF, Ang-1, Ang-2) and in histological assays. The T. cruzi increased the inflammatory and angiogenic mediators in the infected mice when they were compared to non-infected animals. However, the Colombian strain has led to higher (i) leukocyte infiltration, (ii) cardiac TNF and CCL5 production/expression, (iii) cardiac tissue parasitism, and to higher (iv) ratio between heart/body weights. On the other hand, the Colombian strain has caused lower production and expression VEGF, Ang-1 and Ang-2, when it was compared to the Y strain of the parasite. The present study highlights that the T. cruzi-genetic population defines the pattern of angiogenic/inflammatory mediators in the heart tissue, and that it may contribute to the magnitude of the cardiac pathogenesis. Besides, such assumption opens windows to the understanding of the angiogenic mediator's role in association with the experimental T. cruzi infection.