Current understanding of the Trypanosoma cruzi-cardiomyocyte interaction

Abstract

Trypanosoma cruzi, the etiological agent of Chagas disease, exhibits multiple strategies to ensure its establishment and persistence in the host. Although this parasite has the ability to infect different organs, heart impairment is the most frequent clinical manifestation of the disease. Advances in knowledge of T. cruzi–cardiomyocyte interactions have contributed to a better understanding of the biological events involved in the pathogenesis of Chagas disease. This brief review focuses on the current understanding of molecules involved in T. cruzi–cardiomyocyte recognition, the mechanism of invasion, and on the effect of intracellular development of T. cruzi on the structural organization and molecular response of the target cell.

Inhibition of Cyclooxygenase-1 and Cyclooxygenase-2 Impairs Trypanosoma cruzi Entry into Cardiac Cells and Promotes Differential Modulation of the Inflammatory Response

“…This is a significant finding, because trypomastigotes are the T. cruzi life cycle stages that are capable of invading host cells through a Ca 2ϩ -dependent lysosome recruitment process, which involves parasite-mediated signaling (22). Elevation of intracellular Ca 2ϩ levels has also been demonstrated in T. cruzi-infected cardiac cells (4).…”

“…High levels of 15-epi-LXA 4 were observed in T. cruzi-infected mice treated with the low doses of ASA, while high ASA doses decreased 15-epi-LXA 4 levels (37). Importantly, 15-epi-LXA 4 prevented parasitemia, mortality, and cardiac changes in vivo and restored the protective role in the treatment group that received a high dose of ASA (37).…”

“…cruzi induces upregulation of nitric oxide (NO) production in cardiomyocytes along with an upregulation in the levels of interleukin-6 (IL-6), IL-1␤, tumor necrosis factor alpha (TNF-␣), and transforming growth factor ␤ (TGF-␤) (8)(9)(10)(11)(12)(13). The resulting acute myocarditis is characterized by an intense inflammatory response typified by upregulation of inflammatory mediators, such as cytokines, chemokines, inducible nitric oxide synthase (iNOS), and endothelin (7), and also eicosanoids (10), which are essential elements to the defensive reaction in cardiac tissue (4), and it can also result in cardiac hypertrophy (8,9).…”

“…Although T. cruzi trypomastigotes are broadly dispersed among many different organs in the mammalian host, cardiac tissue is an important target for this parasite, and the T. cruzicardiomyocyte interaction has been the subject of intense investigation (4)(5)(6)(7).…”

Molecular mechanisms of myocarditis caused by Trypanosoma cruzi

“…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].…”