Trypanosoma cruzi Infection Induces a Global Host Cell Response in Cardiomyocytes

Abstract

Chagas' disease, caused by the hemoflagellate protozoan Trypanosoma cruzi, affects millions of people in South and Central America. Chronic chagasic cardiomyopathy, the most devastating manifestation of this disease, occurs in approximately one-third of infected individuals. Events associated with the parasite's tropism for and invasion of cardiomyocytes have been the focus of intense investigation in recent years. In the present study, we use murine microarrays to investigate the cellular response caused by invasion of primary murine cardiomyocytes by T. cruzi trypomastigotes. These studies identified 353 murine genes that were differentially expressed during the early stages of invasion and infection of these cells. Genes associated with the immune response, inflammation, cytoskeleton organization, cell-cell and cell-matrix interactions, apoptosis, cell cycle, and oxidative stress are among those affected during the infection. Our data indicate that T. cruzi induces broad modulations of the host cell machinery in ways that provide insight into how the parasite survives, replicates, and persists in the infected host and ultimately defines the clinical outcome of the infection.

Matrix Metalloproteinases 2 and 9 Are Differentially Expressed in Patients with Indeterminate and Cardiac Clinical Forms of Chagas Disease

“…5B). T. cruzi-infected cardiomyocytes elicit a strong immune response, characterized by the production of IL-1␤ and TNF-␣, which is associated with the hypertrophic effect in these cells (45). Moreover, MMP-9 can cleave and activate these cytokines and thus intensify the process of cardiac remodeling (8,45,46).…”

“…T. cruzi-infected cardiomyocytes elicit a strong immune response, characterized by the production of IL-1␤ and TNF-␣, which is associated with the hypertrophic effect in these cells (45). Moreover, MMP-9 can cleave and activate these cytokines and thus intensify the process of cardiac remodeling (8,45,46). Heart failure is characterized by activation of different cytokines and enzymes, including MMPs, which have been implicated in the left ventricular remodeling common to different heart failure etiologies (38,47,48).…”

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

“…This information provides insights into how the parasite survives, replicates, and persists in the infected host and ultimately the clinical outcome of the infection (5).…”

“…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).…”

Chagasic Cardiomyopathy

“…Microarray studies of T. cruzi acute infection in mouse cardiomyocytes showed a regulation of 353 genes (111 up regulated and 242 down regulated) associated with inflammation, cytoskeleton, cell interaction, apoptosis, cell cycle, and oxidative stress. Interestingly, early genes up regulated include a vast range of chemokines, which attract mononuclear cells (Manque et al, 2011). In consequence, there is cell destruction (myocytolysis), interstitial edema, hypertrophy of myocardial fibers, and alteration of the cardiac microcirculation with platelet aggregation, production of pro-inflammatory cytokines and expression of vascular adhesion molecules by endothelial cells (Rossi et al, 2010).…”