Toll-like receptor 2 mediates Staphylococcus aureus-induced myocardial dysfunction and cytokine production in the heart

Circulation. 2004 Dec 14;110(24):3693-8. doi: 10.1161/01.CIR.0000143081.13042.04. Epub 2004 Nov 29.


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-1beta, 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-kappaB, 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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Child
  • Cyclic GMP / biosynthesis
  • Cytokines / biosynthesis*
  • Heart / physiopathology
  • Humans
  • Interleukin-1 / biosynthesis
  • Mice
  • Mice, Knockout
  • Myocardial Contraction
  • Myocardium / metabolism*
  • Nitric Oxide / biosynthesis
  • Receptors, Cell Surface / genetics
  • Receptors, Cell Surface / physiology*
  • Signal Transduction
  • Staphylococcal Infections / complications*
  • Staphylococcus aureus / isolation & purification
  • Staphylococcus aureus / pathogenicity*
  • Toll-Like Receptor 2
  • Tumor Necrosis Factor-alpha / biosynthesis
  • Ventricular Dysfunction, Left / etiology
  • Ventricular Dysfunction, Left / metabolism*
  • Ventricular Dysfunction, Left / physiopathology*


  • Cytokines
  • Interleukin-1
  • Receptors, Cell Surface
  • Tlr2 protein, mouse
  • Toll-Like Receptor 2
  • Tumor Necrosis Factor-alpha
  • Nitric Oxide
  • Cyclic GMP