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


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.
Knuefermann
Pascal
P
Department of Pediatrics, Baylor College of Medicine and Texas Children's Hospital, Houston, Tex, USA.
Sakata
Yasushi
Y
Baker
J Scott
JS
Huang
Chien-Hua
CH
Sekiguchi
Kenichi
K
Hardarson
Hordur S
HS
Takeuchi
Osamu
O
Akira
Shizuo
S
Vallejo
Jesus G
JG
D000818:Animals; D002648:Child; D006152:Cyclic GMP / Q000096:biosynthesis; D016207:Cytokines / Q000096:biosynthesis*; D006321:Heart / Q000503:physiopathology; D006801:Humans; D007375:Interleukin-1 / Q000096:biosynthesis; D051379:Mice; D018345:Mice, Knockout; D009200:Myocardial Contraction; D009206:Myocardium / Q000378:metabolism*; D009569:Nitric Oxide / Q000096:biosynthesis; D011956:Receptors, Cell Surface / Q000235:genetics / Q000502:physiology*; D015398:Signal Transduction; D013203:Staphylococcal Infections / Q000150:complications*; D013211:Staphylococcus aureus / Q000302:isolation & purification / Q000472:pathogenicity*; D051195:Toll-Like Receptor 2; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis; D018487:Ventricular Dysfunction, Left / Q000209:etiology / Q000378:metabolism* / Q000503:physiopathology*
D016207:Cytokines; D007375:Interleukin-1; D011956:Receptors, Cell Surface; C493486:Tlr2 protein, mouse; D051195:Toll-Like Receptor 2; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; D006152:Cyclic GMP