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Toll-like receptor 2 regulates interleukin-1beta-dependent cardiomyocyte hypertrophy triggered by Trypanosoma cruzi
Christine A Petersen1, Katherine A Krumholz, Barbara A Burleigh
1Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, MA 02115, USA.
Abstract:
Trypanosoma cruzi, the intracellular protozoan parasite that causes Chagasic cardiomyopathy, elicits a robust hypertrophic response in isolated cardiomyocytes. Previous studies established that T. cruzi-elicited cardiomyocyte hypertrophy is mediated by interleukin-1beta produced by infected cardiomyocyte cultures. Here, we define key upstream signaling events leading to cardiomyocyte hypertrophy in response to T. cruzi infection, to be dependent on Toll-like receptor 2 and NF-kappaB. Furthermore, we demonstrate that cardiomyocyte hypertrophy, which is initiated by live infective T. cruzi trypomastigotes or stimulation of isolated myocytes with secreted/released trypomastigote molecules, is a common outcome of the cardiomyocyte recognition of pathogen-associated molecular patterns by intrinsic Toll-like receptors. This study is the first to link pathogen recognition by intrinsic Toll-like receptors to cardiomyocyte hypertrophy.
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