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Cutting Edge: Cardiac Myosin Activates Innate Immune Responses through TLRs¹

Department of Microbiology and Immunology, University of Oklahoma Health Sciences Center, Biomedical Research Center, Oklahoma City, OK 73104

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.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

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

⁵ Abbreviations used in this paper: DCM, dilated cardiomyopathy; HCM, human cardiac myosin; hTLR, human TLR; PAMP, pathogen-associated molecular pattern; siRNA, small interfering RNA; SKM, skeletal myosin.

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