Key result
Bacterial flagellin triggered cardiac innate immune responses and provoked reversible myocardial dysfunction, characterized by reduced ejection fraction and decreased end-systolic elastance.
Why the study?
Does bacterial flagellin trigger cardiac innate immune responses and acute contractile dysfunction in preclinical models?
Does bacterial flagellin trigger cardiac innate immune responses and acute contractile dysfunction in preclinical models?
Bacterial flagellin directly triggers cardiac innate immune responses and acute, reversible myocardial contractile dysfunction, suggesting a mechanism for septic cardiomyopathy.
May implicate flagellin in septic cardiomyopathy; hypothesis-generating in animals and leaves open human translation.
BACKGROUND: Myocardial contractile failure in septic shock may develop following direct interactions, within the heart itself, between molecular motifs released by pathogens and their specific receptors, notably those belonging to the toll-like receptor (TLR) family. Here, we determined the ability of bacterial flagellin, the ligand of mammalian TLR5, to trigger myocardial inflammation and contractile dysfunction. METHODOLOGY/PRINCIPAL FINDINGS: TLR5 expression was determined in H9c2 cardiac myoblasts, in primary rat cardiomyocytes, and in whole heart extracts from rodents and humans. The ability of flagellin to activate pro-inflammatory signaling pathways (NF-kappaB and MAP kinases) and the expression of inflammatory cytokines was investigated in H9c2 cells, and, in part, in primary cardiomyocytes, as well as in the mouse myocardium in vivo. The influence of flagellin on left ventricular function was evaluated in mice by a conductance pressure-volume catheter. Cardiomyocytes and intact myocardium disclosed significant TLR5 expression. In vitro, flagellin activated NF-kappaB, MAP kinases, and the transcription of inflammatory genes. In vivo, flagellin induced cardiac activation of NF-kappaB, expression of inflammatory cytokines (TNF alpha, IL-1 beta, IL-6, MIP-2 and MCP-1), and provoked a state of reversible myocardial dysfunction, characterized by cardiac dilation, reduced ejection fraction, and decreased end-systolic elastance. CONCLUSION/SIGNIFICANCE: These results are the first to indicate that flagellin has the ability to trigger cardiac innate immune responses and to acutely depress myocardial contractility.
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Rolli et al. (2010) studied Myocardial contractile dysfunction in sepsis. Bacterial flagellin vs. Vehicle (saline) was evaluated on Myocardial contractile function and inflammatory cytokine expression (p=<0.05). Bacterial flagellin triggered cardiac innate immune responses and provoked reversible myocardial dysfunction, characterized by reduced ejection fraction and decreased end-systolic elastance.
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