This Article Full Text Full Text (PDF) All Versions of this Article: 110/24/3693    most recent 01.CIR.0000143081.13042.04v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Knuefermann, P. Articles by Vallejo, J. G. Search for Related Content PubMed PubMed Citation Articles by Knuefermann, P. Articles by Vallejo, J. G. Pubmed/NCBI databases Gene GEO Profiles HomoloGene UniGene Compound via MeSH Substance via MeSH Hazardous Substances DB NITRIC OXIDE Medline Plus Health Information Staphylococcal Infections Related Collections Contractile function Animal models of human disease Gene expression

(Circulation. 2004;110:3693-3698.)
© 2004 American Heart Association, Inc.

Molecular Cardiology

Toll-Like Receptor 2 Mediates Staphylococcus aureus–Induced Myocardial Dysfunction and Cytokine Production in the Heart

Pascal Knuefermann, MD^*; Yasushi Sakata, MD, PhD^*; J. Scott Baker, BS; Chien-Hua Huang, MD; Kenichi Sekiguchi, MD, PhD; Hordur S. Hardarson, MD; Osamu Takeuchi, MD, PhD; Shizuo Akira, MD, PhD; Jesus G. Vallejo, MD

From the Department of Pediatrics (P.K., J.S.B., C.-H.H., H.S.H., J.G.V.), Section of Infectious Diseases, and the Winters Center for Heart Failure Research (P.K., Y.S., S.-H.H., K.S., J.G.V.), Baylor College of Medicine and Texas Children’s Hospital, Houston, Tex, and the Department of Host Defense (O.T., S.A.), Osaka University, Osaka, Japan.

Correspondence to Jesus G. Vallejo, MD, 6621 Fannin St, Houston, TX 77030. E-mail jvallejo{at}bcm.tmc.edu

Received June 17, 2004; revision received July 12, 2004; accepted August 2, 2004.

Background— Staphylococcus aureus sepsis is associated with significant myocardial dysfunction. Toll-like receptor 2 (TLR2) mediates the inflammatory response to S aureus and may trigger an innate immune response in the heart. We hypothesized that a TLR2 deficiency would attenuate S aureus–induced cardiac proinflammatory mediator production and the development of cardiac dysfunction.

Methods and Results— Wild-type and TLR2-deficient (TLR2D) mice were studied. S aureus challenge significantly increased tumor necrosis factor, interleukin-1ß, and nitric oxide expression in hearts of wild-type mice. This response was significantly blunted in TLR2D mice. Hearts from TLR2D mice had impaired S aureus–induced activation of interleukin-1 receptor–associated kinase, c-Jun NH₂ terminal kinase, nuclear factor-B, and activator protein-1. Moreover, hearts from TLR2D mice were protected against S aureus–induced contractile dysfunction.

Conclusions— These results show for the first time that TLR2 signaling contributes to the loss of myocardial contractility and cytokine production in the heart during S aureus sepsis.

Key Words: inflammation • infection • immune system • myocardial contraction

This article has been cited by other articles:

				H. S. Deshmukh, J. B. Hamburger, S. H. Ahn, D. G. McCafferty, S. R. Yang, and V. G. Fowler Jr. Critical Role of NOD2 in Regulating the Immune Response to Staphylococcus aureus Infect. Immun., April 1, 2009; 77(4): 1376 - 1382. [Abstract] [Full Text] [PDF]

				W. Chao Toll-like receptor signaling: a critical modulator of cell survival and ischemic injury in the heart Am J Physiol Heart Circ Physiol, January 1, 2009; 296(1): H1 - H12. [Abstract] [Full Text] [PDF]

				P. Knuefermann, M. Schwederski, M. Velten, P. Krings, H. Ehrentraut, M. Rudiger, O. Boehm, K. Fink, U. Dreiner, C. Grohe, et al. Bacterial DNA induces myocardial inflammation and reduces cardiomyocyte contractility: role of Toll-like receptor 9 Cardiovasc Res, April 1, 2008; 78(1): 26 - 35. [Abstract] [Full Text] [PDF]

				J. H. Boyd, S. Mathur, Y. Wang, R. M. Bateman, and K. R. Walley Toll-like receptor stimulation in cardiomyoctes decreases contractility and initiates an NF-{kappa}B dependent inflammatory response Cardiovasc Res, December 1, 2006; 72(3): 384 - 393. [Abstract] [Full Text] [PDF]

				Y. Sun, A. G. Hise, C. M. Kalsow, and E. Pearlman Staphylococcus aureus-Induced Corneal Inflammation Is Dependent on Toll-Like Receptor 2 and Myeloid Differentiation Factor 88 Infect. Immun., September 1, 2006; 74(9): 5325 - 5332. [Abstract] [Full Text] [PDF]

				U. Grandel, M. Hopf, M. Buerke, K. Hattar, M. Heep, L. Fink, R. M. Bohle, S. Morath, T. Hartung, S. Pullamsetti, et al. Mechanisms of Cardiac Depression Caused by Lipoteichoic Acids From Staphylococcus aureus in Isolated Rat Hearts Circulation, August 2, 2005; 112(5): 691 - 698. [Abstract] [Full Text] [PDF]

				B. Fournier and D. J. Philpott Recognition of Staphylococcus aureus by the Innate Immune System Clin. Microbiol. Rev., July 1, 2005; 18(3): 521 - 540. [Abstract] [Full Text] [PDF]