Published Online
on November 29, 2004

A more recent version of this article appeared on December 14, 2004

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Submitted on June 17, 2004
Revised on July 12, 2004
Accepted on August 2, 2004

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, and 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.

^* To whom correspondence should be addressed. E-mail: jvallejo{at}bcm.tmc.edu.

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-1, 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

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