Marcos Lopez1, Herbert B Tanowitz2, Nisha J Garg3. 1. Translational Biomedical Research Group, Fundación Cardiovascular de Colombia, Floridablanca, Colombia and Graduate Program in Biomedical Sciencies, Faculty of Health, Universidad del Valle, Cali, Colombia. 2. Departments of Pathology and Medicine, Albert Einstein College of Medicine, Bronx, New York. 3. Departments of Microbiology and Immunology and Pathology, Institute for Human Infections and Immunity, University of Texas Medical Branch, Galveston, Texas 77555-1070.
Abstract
PURPOSE OF REVIEW: Trypanosoma cruzi is the causative agent of Chagas disease. Decades after initial infection, ~30% of individuals can develop chronic chagasic cardiomyopathy. There are several proposed mechanisms for pathogenesis of Chagas disease, including parasite persistence, immune responses against parasite or self that continue in the heart, vascular compromise, and involvement of autonomous and central nervous system. Herein, we will focus on the significance of macrophages, mitochondrial dysfunction, and oxidative stress in progression of chagasic cardiomyopathy. RECENT FINDINGS: The current literature suggests that T. cruzi prevents cytotoxic activities of the innate immune cells and persists in the host, contributing to mitochondrial oxidative stress. We discuss how the neoantigens generated due to cellular oxidative damage contribute to chronic inflammatory stress in chagasic disease. SUMMARY: We propose that metabolic regulators, PARP-1/SIRT1, determine the disease outcome by modulating the mitochondrial and macrophage stress and antioxidant/oxidant imbalance, and offer a potential new therapy against chronic Chagas disease.
PURPOSE OF REVIEW: Trypanosoma cruzi is the causative agent of Chagas disease. Decades after initial infection, ~30% of individuals can develop chronic chagasic cardiomyopathy. There are several proposed mechanisms for pathogenesis of Chagas disease, including parasite persistence, immune responses against parasite or self that continue in the heart, vascular compromise, and involvement of autonomous and central nervous system. Herein, we will focus on the significance of macrophages, mitochondrial dysfunction, and oxidative stress in progression of chagasic cardiomyopathy. RECENT FINDINGS: The current literature suggests that T. cruzi prevents cytotoxic activities of the innate immune cells and persists in the host, contributing to mitochondrial oxidative stress. We discuss how the neoantigens generated due to cellular oxidative damage contribute to chronic inflammatory stress in chagasic disease. SUMMARY: We propose that metabolic regulators, PARP-1/SIRT1, determine the disease outcome by modulating the mitochondrial and macrophage stress and antioxidant/oxidant imbalance, and offer a potential new therapy against chronic Chagas disease.
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