Abstract
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.
Footnotes
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↵1 This study was supported by National Heart, Lung, and Blood Institute (NHLBI) Grant R01 HL56267. M.W.C. is the recipient of a NHLBI merit award HL35280.
↵2 P.Z., C.J.C., and K.M.A. contributed equally to this study.
↵3 Current address: Division of Pediatric Allergy and Immunology, Duke University Medical Center, 109 Medical Sciences Research Building I, Research Drive, Durham, NC 27710.
↵4 Address correspondence and reprint requests to Dr. Madeleine W. Cunningham, Department of Microbiology and Immunology, University of Oklahoma Health Sciences Center, Biomedical Research Center, Room 217, 975 Northeast 10th Street, Oklahoma City, OK 73104. E-mail address: madeleine-cunningham{at}ouhsc.edu
- Received March 28, 2008.
- Accepted May 7, 2009.
- Copyright © 2009 by The American Association of Immunologists, Inc.
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