Cardiovascular Research Advance Access first published online on January 14, 2008
This version [Corrected Proof] published online on February 27, 2008
Cardiovascular Research, doi:10.1093/cvr/cvn011
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Bacterial DNA induces myocardial inflammation and reduces cardiomyocyte contractility: role of Toll-like receptor 9
1 Department for Anesthesiology and Intensive Care Medicine, University Hospital Bonn, Sigmund-Freud-Strasse 25, Bonn 53105, Germany
2 Institute of Physiology II, University Hospital Bonn, Bonn, Germany
3 Department of Pharmacology and Toxicology, University Hospital Bonn, Bonn, Germany
4 Department of Internal Medicine 2, University Hospital Bonn, Bonn, Germany
5 Molecular Cardioprotection and Inflammation Group, Department of Anaesthesia, Bristol Royal Infirmary, Bristol, UK
* Corresponding author. Tel: +49 228 2871 4110; fax: +49 228 2871 4115. E-mail address: pascal.knuefermann{at}ukb.uni-bonn.de
Aims: Myocardial function is severely compromised during sepsis. Several underlying mechanisms have been proposed. The innate immune system, i.e. Toll-like receptor (TLR) 2 and 4, significantly contributes to cardiac dysfunction. Little is known regarding TLR9 and its pathogenic ligand bacterial DNA in the myocardium. We therefore studied the role of TLR9 in myocardial inflammation and cardiac contractility.
Methods and results: Wild-type (WT, C57BL/6) and TLR9-deficient (TLR9-D) mice and isolated cardiomyocytes were challenged with synthetic bacterial DNA (CpG-ODN). Myocardial contractility as well as markers of inflammation/signalling were determined. Isolated cardiomyocytes incorporated fluorescence-marked CpG-ODN. In WT mice, CpG-ODN caused a robust response in hearts demonstrated by increased levels of tumour necrosis factor (TNF-
), interleukin (IL)-1β, IL-6, inducible nitric oxide synthase (iNOS), and nuclear factor 
B activity. This inflammatory response was absent in TLR9-D mice. Under similar conditions, contractility measurements of isolated ventricular cardiomyocytes demonstrated a TLR9-dependent loss of sarcomeric shortening after CpG-ODN exposure. This observation was iNOS dependent as the application of a specific iNOS inhibitor reversed sarcomeric shortening to normal levels.
Conclusion: Our data suggest that bacterial DNA contributes to myocardial cytokine production and loss of cardiomyocyte contractility via TLR9.
KEYWORDS Sepsis; Contractile function; Infection/inflammation; Cardiomyocytes
Time for primary review: 24 days
These two authors contributed equally to this work.
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Cardiovasc Res 2008 78: 3-4.
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