Limits...
Toll-like receptor 9 promotes cardiac inflammation and heart failure during polymicrobial sepsis.

Lohner R, Schwederski M, Narath C, Klein J, Duerr GD, Torno A, Knuefermann P, Hoeft A, Baumgarten G, Meyer R, Boehm O - Mediators Inflamm. (2013)

Bottom Line: 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.This coincided with reduced cardiomyocyte sarcomere shortening.TLR9 deficiency resulted in significant reduction of cardiac inflammation and a sustained heart function.

View Article: PubMed Central - PubMed

Affiliation: Institute for Physiology II, University of Bonn, Nussallee 11, 53115 Bonn, Germany.

ABSTRACT

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.

Show MeSH

Related in: MedlinePlus

Immune receptor profile in WT hearts. (a)–(e) Messenger RNA levels of TLR2, 4, and 9, CD-14 (a)–(d), and TREM1 (e) were analysed 6, 18, 24, and 36 h after sepsis induction. Untreated WT mice served as control (a)–(e) (*:P < 0.05;  n = 10/group; mean  ±  SEM).
© Copyright Policy - open-access
Related In: Results  -  Collection


getmorefigures.php?uid=PMC3713595&req=5

fig3: Immune receptor profile in WT hearts. (a)–(e) Messenger RNA levels of TLR2, 4, and 9, CD-14 (a)–(d), and TREM1 (e) were analysed 6, 18, 24, and 36 h after sepsis induction. Untreated WT mice served as control (a)–(e) (*:P < 0.05;  n = 10/group; mean  ±  SEM).

Mentions: Eighteen hours after CASP TLR2 and CD14 were significantly upregulated (TLR2: versus control P = 0.0011, Figure 3(a); CD14: versus control 0.0003, Figure 3(d)). Toll-like receptor 4 was increased 18, 24, and 36 h after CASP (all versus control P = 0.0067, P = 0.0092, P = 0.0001, Figure 3(b)), whereas TLR9 was elevated only 36 h after infection (versus control P = 0.0029, Figure 3(c)). Triggering receptor expressed on myeloid cells 1 (TREM1) mRNA increased continuously reaching the level of significance after 36 h (versus control P = 0.0115, Figure 3(e)).


Toll-like receptor 9 promotes cardiac inflammation and heart failure during polymicrobial sepsis.

Lohner R, Schwederski M, Narath C, Klein J, Duerr GD, Torno A, Knuefermann P, Hoeft A, Baumgarten G, Meyer R, Boehm O - Mediators Inflamm. (2013)

Immune receptor profile in WT hearts. (a)–(e) Messenger RNA levels of TLR2, 4, and 9, CD-14 (a)–(d), and TREM1 (e) were analysed 6, 18, 24, and 36 h after sepsis induction. Untreated WT mice served as control (a)–(e) (*:P < 0.05;  n = 10/group; mean  ±  SEM).
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3713595&req=5

fig3: Immune receptor profile in WT hearts. (a)–(e) Messenger RNA levels of TLR2, 4, and 9, CD-14 (a)–(d), and TREM1 (e) were analysed 6, 18, 24, and 36 h after sepsis induction. Untreated WT mice served as control (a)–(e) (*:P < 0.05;  n = 10/group; mean  ±  SEM).
Mentions: Eighteen hours after CASP TLR2 and CD14 were significantly upregulated (TLR2: versus control P = 0.0011, Figure 3(a); CD14: versus control 0.0003, Figure 3(d)). Toll-like receptor 4 was increased 18, 24, and 36 h after CASP (all versus control P = 0.0067, P = 0.0092, P = 0.0001, Figure 3(b)), whereas TLR9 was elevated only 36 h after infection (versus control P = 0.0029, Figure 3(c)). Triggering receptor expressed on myeloid cells 1 (TREM1) mRNA increased continuously reaching the level of significance after 36 h (versus control P = 0.0115, Figure 3(e)).

Bottom Line: 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.This coincided with reduced cardiomyocyte sarcomere shortening.TLR9 deficiency resulted in significant reduction of cardiac inflammation and a sustained heart function.

View Article: PubMed Central - PubMed

Affiliation: Institute for Physiology II, University of Bonn, Nussallee 11, 53115 Bonn, Germany.

ABSTRACT

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.

Show MeSH
Related in: MedlinePlus