Toll-like receptor 2 regulates interleukin-1beta-dependent cardiomyocyte hypertrophy triggered by Trypanosoma cruzi.
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.
Petersen
Christine A
CA
Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, MA 02115, USA.
Krumholz
Katherine A
KA
Burleigh
Barbara A
BA
D000818:Animals; D048429:Cell Size; D002478:Cells, Cultured; D007375:Interleukin-1 / Q000378:metabolism*; D032383:Myocytes, Cardiac / Q000166:cytology / Q000378:metabolism / Q000469:parasitology*; D016328:NF-kappa B / Q000378:metabolism; D051381:Rats; D015398:Signal Transduction; D014349:Trypanosoma cruzi
D007375:Interleukin-1; D016328:NF-kappa B