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1.
Parasitol Int ; 83: 102345, 2021 Aug.
Article in English | MEDLINE | ID: mdl-33857596

ABSTRACT

Chagas disease, caused by Trypanosoma cruzi, is a major neglected tropical disease that occurs mainly as chronic infection and systemic infection. Currently, there is no suitable and effective drug to treat this parasitic disease. Administration of nutrients with immunomodulatory properties, such as arginine and nitric oxide radicals, may be helpful as antiparasitic therapy. In this study, we evaluated the effects of arginine supplementation during the acute phase of infection under the development of chronic Chagas' heart disease in Swiss mice inoculated with the Berenice-78 strain of T. cruzi. The effectiveness of arginine was determined by daily detection of the parasite in the blood and long-term serum levels of nitric oxide and tumor necrosis factor-alpha, in addition to evaluation of heart tissue damage. Arginine could flatten parasitemia and prevent elevation of tumor necrosis factor-alpha in T. cruzi-infected mice. Regarding chronic inflammatory myocardial derangements, similar findings were verified among T. cruzi-infected groups. Arginine promoted collagenogenesis in the heart muscle tissue of T. cruzi-infected arginine-supplemented group. These data show the paradoxical benefits of arginine in improving the outcome of Chagas chronic cardiomyopathy.


Subject(s)
Arginine/metabolism , Chagas Cardiomyopathy/pathology , Collagen/physiology , Heart/parasitology , Trypanocidal Agents/pharmacology , Trypanosoma cruzi/drug effects , Animal Feed/analysis , Animals , Arginine/administration & dosage , Arginine/pharmacology , Chagas Cardiomyopathy/drug therapy , Chagas Cardiomyopathy/parasitology , Diet , Dietary Supplements/analysis , Heart/drug effects , Mice , Trypanocidal Agents/administration & dosage , Trypanocidal Agents/metabolism
2.
Infect Immun ; 88(4)2020 03 23.
Article in English | MEDLINE | ID: mdl-31907197

ABSTRACT

Chagas disease, caused by Trypanosoma cruzi, is a major public health issue. Limitations in immune responses to natural T. cruzi infection usually result in parasite persistence with significant complications. A safe, effective, and reliable vaccine would reduce the threat of T. cruzi infections; however, no suitable vaccine is currently available due to a lack of understanding of the requirements for induction of fully protective immunity. We established a T. cruzi strain expressing green fluorescent protein (GFP) under the control of dihydrofolate reductase degradation domain (DDD) with a hemagglutinin (HA) tag, GFP-DDDHA, which was induced by trimethoprim-lactate (TMP-lactate), which results in the death of intracellular parasites. This attenuated strain induces very strong protection against reinfection. Using this GFP-DDDHA strain, we investigated the mechanisms underlying the protective immune response in mice. Immunization with this strain led to a response that included high levels of gamma interferon (IFN-γ) and tumor necrosis factor alpha (TNF-α), as well as a rapid expansion of effector and memory T cells in the spleen. More CD8+ T cells differentiate to memory cells following GFP-DDDHA infection than after infection with a wild-type (WT) strain. The GFP-DDDHA strain also provides cross-protection against another T. cruzi isolate. IFN-γ is important in mediating the protection, as IFN-γ knockout (KO) mice failed to acquire protection when infected with the GFP-DDDHA strain. Immune cells demonstrated earlier and stronger protective responses in immunized mice after reinfection with T. cruzi than those in naive mice. Adoptive transfers with several types of immune cells or with serum revealed that several branches of the immune system mediated protection. A combination of serum and natural killer cells provided the most effective protection against infection in these transfer experiments.


Subject(s)
Chagas Disease/prevention & control , Protozoan Vaccines/immunology , T-Lymphocyte Subsets/immunology , Trypanosoma cruzi/immunology , Animals , Chagas Disease/immunology , Disease Models, Animal , Immunity, Cellular , Immunologic Factors/metabolism , Interferon-gamma/metabolism , Mice , Protozoan Vaccines/administration & dosage , Tumor Necrosis Factor-alpha/metabolism , Vaccines, Attenuated/administration & dosage , Vaccines, Attenuated/immunology
3.
Infect Immun ; 86(4)2018 04.
Article in English | MEDLINE | ID: mdl-29358332

ABSTRACT

Trypanosoma cruzi is a protozoan parasite that causes Chagas disease (CD). CD is a persistent, lifelong infection affecting many organs, most notably the heart, where it may result in acute myocarditis and chronic cardiomyopathy. The pathological features include myocardial inflammation and fibrosis. In the Brazil strain-infected CD-1 mouse, which recapitulates many of the features of human infection, we found increased plasma levels of resolvin D1 (RvD1), a specialized proresolving mediator of inflammation, during both the acute and chronic phases of infection (>100 days postinfection) as determined by enzyme-linked immunosorbent assay (ELISA). Additionally, ELISA on lysates of trypomastigotes of both strains Tulahuen and Brazil revealed elevated levels of RvD1 compared with lysates of cultured epimastigotes of T. cruzi, tachyzoites of Toxoplasma gondii, trypomastigotes of Trypanosoma brucei, cultured L6E9 myoblasts, and culture medium containing no cells. Lysates of T. cruzi-infected myoblasts also displayed increased levels of RvD1. Lipid mediator metabolomics confirmed that the trypomastigotes of T. cruzi produced RvD1, RvD5, and RvE2, which have been demonstrated to modulate the host response to bacterial infections. Plasma RvD1 levels may be both host and parasite derived. Since T. cruzi synthesizes specialized proresolving mediators of inflammation, as well as proinflammatory eicosanoids, such as thromboxane A2, one may speculate that by using these lipid mediators to modulate its microenvironment, the parasite is able to survive.


Subject(s)
Chagas Disease/metabolism , Chagas Disease/parasitology , Docosahexaenoic Acids/metabolism , Eicosapentaenoic Acid/analogs & derivatives , Trypanosoma cruzi/metabolism , Biomarkers , Cardiac Imaging Techniques , Chagas Disease/diagnosis , Chagas Disease/immunology , Chromatography, Liquid , Docosahexaenoic Acids/blood , Eicosapentaenoic Acid/blood , Eicosapentaenoic Acid/metabolism , Host-Parasite Interactions/immunology , Immunomodulation , Lipid Metabolism , Metabolome , Prostaglandins/metabolism , Tandem Mass Spectrometry , Trypanosoma cruzi/immunology
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