Bacterial flagellin triggers cardiac innate immune responses and acute contractile dysfunction

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...

Full description

Saved in:
Bibliographic Details
Published in:PloS one 2010-09, Vol.5 (9), p.e12687-e12687
Main Authors: Rolli, Joelle, Rosenblatt-Velin, Nathalie, Li, Jianhui, Loukili, Noureddine, Levrand, Sandra, Pacher, Pal, Waeber, Bernard, Feihl, François, Ruchat, Patrick, Liaudet, Lucas
Format: Article
Language:English
Subjects:
Animals
Apoptosis
Bacteria
Biology
Cardiomyocytes
Cardiovascular Disorders/Heart Failure
Cardiovascular Disorders/Hemodynamics
Catheters
Cell Line
Cells, Cultured
Conductance
Contractility
Cytokines
Cytokines - genetics
Cytokines - immunology
Flagellin
Flagellin - immunology
Gene expression
Gram-negative bacteria
Heart
Heart - physiopathology
Heart diseases
Hostages
Humans
Immune response
Immune system
Immunity, Innate
Immunology/Innate Immunity
Infectious Diseases/Bacterial Infections
Inflammation
Innate immunity
Intensive care
Interleukin 1
Interleukin 6
Kinases
Male
MAP kinase
Medical instruments
Medicine
Mice
Mice, Inbred BALB C
Mice, Knockout
Monocyte chemoattractant protein 1
Muscle contraction
Myoblasts
Myoblasts, Cardiac - immunology
Myocardial Contraction
Myocardium
Myocardium - immunology
Myocytes, Cardiac - immunology
NF- Kappa B protein
NF-kappa B - genetics
NF-kappa B - immunology
NF-κB protein
Pathogens
Phosphorylation
Phosphotransferases
Proteins
Rats
Receptors
Resistance
Rodents
Salmonella - immunology
Salmonella Infections - immunology
Salmonella Infections - microbiology
Salmonella Infections - physiopathology
Sepsis
Septic shock
Shock, Septic - immunology
Shock, Septic - microbiology
Shock, Septic - physiopathology
Signal transduction
Signaling
TLR5 protein
Toll-Like Receptor 5 - genetics
Toll-Like Receptor 5 - immunology
Toll-like receptors
Transcription
Transcription (Genetics)
Tumor necrosis factor
Ventricle
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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. 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. These results are the first to indicate that flagellin has the ability to trigger cardiac innate immune responses and to acutely depress myocardial contractility.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0012687