Role of PPARs inTrypanosoma cruziInfection: Implications for Chagas Disease Therapy

Abstract

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.

Leptin Functions in Infectious Diseases

“…Additionally, Adipose tissue profoundly expressed Peroxisome proliferator-activated receptor (PPAR-γ) along with adiponectin, which exerts an anti-inflammatory effect. The levels of PPAR-γ were also decreased in T. cruzi infected cells, which leads to the reduced secretion of adiponectin and increased inflammatory reactions ( 176 ).…”

Angiotensin II-Induced Egr-1 Expression is Suppressed by Peroxisome Proliferator- Activated Receptor-γ Ligand 15d-PGJ2 in Macrophages

“…For example, 15d-PGJ 2 regulates the expression of TNF-α and MCP-1 in bone marrow-derived monocytes/macrophages via a PPAR-γ-dependent manner [21]. Furthermore, NF-κB is implicated in the inhibitory effects of 15d-PGJ2 on the inflammatory response [32]. However, little is known about the effect of 15d-PGJ 2 on the expression of Egr-1 and its target genes.…”

Molecular mechanisms of myocarditis caused by Trypanosoma cruzi

“…Symptoms range from mild to severe, although most people do not experience symptoms in the acute and in the chronic stage [3,17].…”

“…The acute phase remains for 4-8 weeks and is associated with unspecific symptoms or clinical signals such as prolonged fever, headache, anorexia, vomiting, drowsiness, malaise, hyperemia and oedema at the portal of entry (Romaña's sign or inoculation chagoma), splenomegaly and enlarged lymph nodes [3,4,44]. During the acute phase, the most severe manifestations are myocarditis accompanied by arrhythmias, congestive heart failure and, more rarely, meningoencephalitis [17,45].…”

“…Introduced to the scientific community in 1909 by the Brazilian medical doctor Carlos Justiniano Ribeiro Chagas, American trypanosomiasis, or Chagas disease [1], is an important zoonotic parasitic disease on the American continent and represents a significant public health problem worldwide [2][3][4][5]. This disease was associated with poor living conditions, particularly poor housing and was considered by the WHO [6,7] to be capable of leading to social shame, disability and mortality [8].…”