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Published on: May 6, 2014
Trypanosoma cruzi infection and nuclear factor kappa B activation prevent apoptosis in cardiac cells
Christine A Petersen1, Katherine A Krumholz, John Carmen
1Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, MA 02115, USA. kalicat@iastate.edu
Insights
Trypanosoma cruzi infection protects heart cells from apoptosis by activating NF-kappaB, a key factor in persistent infection and reduced cardiac damage. This parasite manipulation of cell death pathways is crucial for Chagas disease progression.
Area of Science:
- Cardiovascular Science
- Infectious Diseases
- Cell Biology
Background:
- Cardiomyocyte apoptosis is a critical factor in heart failure and cardiac pathology.
- Trypanosoma cruzi infection causes heart disease and affects host apoptotic pathways differently across cell types.
- While T. cruzi protects neurons and cardiomyocytes from apoptosis, it triggers apoptosis in T cells.
Purpose of the Study:
- To investigate the mechanism by which T. cruzi protects cardiomyocytes from apoptosis.
- To determine the role of NF-kappaB and caspase 3 in T. cruzi-mediated apoptosis resistance in cardiac cells.
Main Methods:
- In vitro culture of cardiomyocytes infected with T. cruzi.
- Induction of apoptosis using tumor necrosis factor alpha and serum reduction.
- Analysis of NF-kappaB activation and caspase 3 activity.
Main Results:
- T. cruzi infection protected cardiomyocytes from apoptosis, correlating with intracellular parasite presence.
- Protection involved the activation of host cell NF-kappaB.
- Apoptotic block by T. cruzi diminished caspase 3 activation.
Conclusions:
- T. cruzi's ability to prevent cardiomyocyte apoptosis is vital for establishing persistent heart infection.
- This mechanism may minimize cardiac damage and remodeling associated with cardiomyocyte apoptosis in cardiovascular disease.
- Understanding this interaction is key for managing Chagas disease cardiomyopathy.
Abstract:
Studies of cardiac pathology and heart failure have implicated cardiomyocyte apoptosis as a critical determinant of disease. Recent evidence indicates that the intracellular protozoan parasite Trypanosoma cruzi, which causes heart disease in chronically infected individuals, impinges on host apoptotic pathways in a cell type-dependent manner. T. cruzi infection of isolated neuronal cells and cardiomyocytes protects against apoptotic cell death, whereas apoptosis is triggered in T cells in T. cruzi-infected animals. In this study, we demonstrate that the ability of T. cruzi to protect cardiac cells in vitro from apoptosis triggered by a combination of tumor necrosis factor alpha and serum reduction correlates with the presence of intracellular parasites and involves activation of host cell NF-kappaB. We further demonstrate that the apoptotic block diminishes activation of caspase 3. The ability of T. cruzi to prevent apoptosis of infected cardiomyocytes is likely to play an important role in establishment of persistent infection in the heart while minimizing potential damage and remodeling that is associated with cardiomyocyte apoptosis in cardiovascular disease.
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