Trypanosoma cruzi infection and nuclear factor kappa B activation prevent apoptosis in cardiac cells.
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.
Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, MA 02115, USA. kalicat@iastate.edu
Christine A
CA
Petersen
Katherine A
KA
Krumholz
John
J
Carmen
Anthony P
AP
Sinai
Barbara A
BA
Burleigh
D000818:Animals; D017209:Apoptosis; D002478:Cells, Cultured; D002598:Chagas Cardiomyopathy / Q000469:parasitology / Q000473:pathology; D018482:Muscle, Skeletal / Q000737:chemistry / Q000469:parasitology* / Q000473:pathology; D032383:Myocytes, Cardiac / Q000166:cytology / Q000378:metabolism / Q000469:parasitology*; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014349:Trypanosoma cruzi / Q000378:metabolism / Q000502:physiology*
D016328:NF-kappa B