Toll-Like Receptor 2 Mediates Staphylococcus aureus–Induced Myocardial Dysfunction and Cytokine Production in the Heart
P Knuefermann, Y Sakata, JS Baker, CH Huang… - Circulation, 2004 - Am Heart Assoc
P Knuefermann, Y Sakata, JS Baker, CH Huang, K Sekiguchi, HS Hardarson, O Takeuchi…
Circulation, 2004•Am Heart AssocBackground—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 …
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 …
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-1β, 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-κB, 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.
Am Heart Assoc