Cutting edge: cardiac myosin activates innate immune responses through TLRs.
Autoimmune attack on the heart is linked to host immune responses against cardiac myosin, the most abundant protein in the heart. Although adaptive immunity is required for disease, little is known about innate immune mechanisms. In this study we report that human cardiac myosin (HCM) acted as an endogenous ligand to directly stimulate human TLRs 2 and 8 and to activate human monocytes to release proinflammatory cytokines. In addition, pathogenic epitopes of human cardiac myosin, the S2 fragment peptides S2-16 and S2-28, stimulated TLRs directly and activated human monocytes. Our data suggest that cardiac myosin and its pathogenic T cell epitopes may link innate and adaptive immunity in a novel mechanism that could promote chronic inflammation in the myocardium.
Zhang
Ping
P
Department of Microbiology and Immunology, University of Oklahoma Health Sciences Center, Biomedical Research Center, Oklahoma City, 73104, USA.
Cox
Carol J
CJ
Alvarez
Kathy M
KM
Cunningham
Madeleine W
MW
D024722:Cardiac Myosins / Q000502:physiology*; D002460:Cell Line; D045744:Cell Line, Tumor; D016207:Cytokines / Q000378:metabolism; D020868:Gene Silencing / Q000276:immunology; D006801:Humans; D007113:Immunity, Innate / Q000235:genetics; D018836:Inflammation Mediators / Q000378:metabolism / Q000502:physiology; D009000:Monocytes / Q000276:immunology / Q000378:metabolism; D009205:Myocarditis / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D032383:Myocytes, Cardiac / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D010455:Peptides / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D051195:Toll-Like Receptor 2 / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D051200:Toll-Like Receptor 8 / Q000172:deficiency / Q000235:genetics / Q000502:physiology*
D016207:Cytokines; D018836:Inflammation Mediators; D010455:Peptides; C495342:TLR2 protein, human; C495349:TLR8 protein, human; D051195:Toll-Like Receptor 2; D051200:Toll-Like Receptor 8; D024722:Cardiac Myosins