Chagas disease, which is caused by Trypanosoma cruzi (T. cruzi), remains a substantial public health concern and an important cause of morbidity and mortality in Latin America. T. cruzi infection causes an intense inflammatory response in diverse tissues by triggering local expression of inflammatory mediators, which results in the upregulation of the levels of cytokines and chemokines, and important cardiac alterations in the host, being one of the most characteristic damages of Chagas disease. Therefore, controlling the inflammatory reaction becomes critical for the control of the proliferation of the parasite and of the evolution of Chagas disease. The nuclear receptors known as peroxisome proliferator-activated receptors (PPARs) have emerged as key regulators of lipid metabolism and inflammation. The precise role of PPAR ligands in T. cruzi infection or in Chagas disease is poorly understood. This review summarizes our knowledge about T. cruzi infection as well as about the activation of PPARs and the potential role of their ligands in the resolution of inflammation, with the aim to address a new pharmacological approach to improve the host health. 1. Introduction Chagas disease is widely distributed throughout Latin America, thus causing a serious public health problem. It is considered the parasitic disease that leads to the greatest economic burden in Latin America due to its prolonged chronicity. Reasonably, public control programs normally focus their resources and strategies on the elimination of insect vectors associated with human habitat and relegate the infected patient. Moreover, migration from rural to urban areas has changed the epidemiology of the disease. While in the 1930’s 70% of Latin Americans lived in rural areas, currently about 70% live in urban areas. The infection was primarily rural and became urban transmissible by blood transfusion. In recent decades, the number of donors with positive serology has increased in endemic countries. Thus, there is a need for new strategies to prevent or stop the cardiac consequences of T. cruzi infection, with an affordable cost to the health system and patients. The host responds to invasion by the activation of inflammation and induction of innate and specific immunity. The infectious inflammatory myocarditis generated by T. cruzi induces an inflammatory response that affects the heart tissue and function. Moreover, the immune system can act with autoimmune reaction with infiltration of macrophages and/or cell-damaging attack. Therefore, the anti-inflammatory actions of peroxisome
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