Toll-like receptor 9 promotes cardiac inflammation and heart failure during polymicrobial sepsis.
BACKGROUND
Aim was to elucidate the role of toll-like receptor 9 (TLR9) in cardiac inflammation and septic heart failure in a murine model of polymicrobial sepsis.


METHODS
Sepsis was induced via colon ascendens stent peritonitis (CASP) in C57BL/6 wild-type (WT) and TLR9-deficient (TLR9-D) mice. Bacterial load in the peritoneal cavity and cardiac expression of inflammatory mediators were determined at 6, 12, 18, 24, and 36 h. Eighteen hours after CASP cardiac function was monitored in vivo. Sarcomere length of isolated cardiomyocytes was measured at 0.5 to 10 Hz after incubation with heat-inactivated bacteria.


RESULTS
CASP led to continuous release of bacteria into the peritoneal cavity, an increase of cytokines, and differential regulation of receptors of innate immunity in the heart. Eighteen hours after CASP WT mice developed septic heart failure characterised by reduction of end-systolic pressure, stroke volume, cardiac output, and parameters of contractility. This coincided with reduced cardiomyocyte sarcomere shortening. TLR9 deficiency resulted in significant reduction of cardiac inflammation and a sustained heart function. This was consistent with reduced mortality in TLR9-D compared to WT mice.


CONCLUSIONS
In polymicrobial sepsis TLR9 signalling is pivotal to cardiac inflammation and septic heart failure.
Institute for Physiology II, University of Bonn, Nussallee 11, 53115 Bonn, Germany.
Ralph
R
Lohner
Markus
M
Schwederski
Carolin
C
Narath
Johanna
J
Klein
Georg D
GD
Duerr
Alexandra
A
Torno
Pascal
P
Knuefermann
Andreas
A
Hoeft
Georg
G
Baumgarten
Rainer
R
Meyer
Olaf
O
Boehm
D000818:Animals; D060085:Coinfection / Q000150:complications / Q000503:physiopathology; D016207:Cytokines / Q000378:metabolism; D005786:Gene Expression Regulation; D006321:Heart / Q000503:physiopathology*; D006333:Heart Failure / Q000150:complications / Q000503:physiopathology*; D006439:Hemodynamics; D007113:Immunity, Innate; D007249:Inflammation / Q000378:metabolism* / Q000473:pathology; D008264:Macrophages / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D010538:Peritonitis / Q000473:pathology; D012518:Sarcomeres / Q000378:metabolism; D018805:Sepsis / Q000150:complications / Q000382:microbiology / Q000503:physiopathology*; D015398:Signal Transduction; D013997:Time Factors; D051217:Toll-Like Receptor 9 / Q000378:metabolism*
D016207:Cytokines; C495370:Tlr9 protein, mouse; D051217:Toll-Like Receptor 9