title: Bacterial flagellin triggers cardiac innate immune responses and acute contractile dysfunction.
abstract: 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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  These results are the first to indicate that flagellin has the ability to trigger cardiac innate immune responses and to acutely depress myocardial contractility.
authors.affiliation: Department of Intensive Care Medicine, University Hospital Medical Center and Faculty of Biology and Medicine, Lausanne, Switzerland.
authors.forename: Joelle
authors.initials: J
authors.lastname: Rolli
authors.forename: Nathalie
authors.initials: N
authors.lastname: Rosenblatt-Velin
authors.forename: Jianhui
authors.initials: J
authors.lastname: Li
authors.forename: Noureddine
authors.initials: N
authors.lastname: Loukili
authors.forename: Sandra
authors.initials: S
authors.lastname: Levrand
authors.forename: Pal
authors.initials: P
authors.lastname: Pacher
authors.forename: Bernard
authors.initials: B
authors.lastname: Waeber
authors.forename: François
authors.initials: F
authors.lastname: Feihl
authors.forename: Patrick
authors.initials: P
authors.lastname: Ruchat
authors.forename: Lucas
authors.initials: L
authors.lastname: Liaudet
mesh_terms: D000818:Animals; D002460:Cell Line; D002478:Cells, Cultured; D016207:Cytokines / Q000235:genetics / Q000276:immunology; D005408:Flagellin / Q000276:immunology*; D006321:Heart / Q000503:physiopathology*; D006801:Humans; D007113:Immunity, Innate; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D032386:Myoblasts, Cardiac / Q000276:immunology; D009200:Myocardial Contraction; D009206:Myocardium / Q000276:immunology*; D032383:Myocytes, Cardiac / Q000276:immunology; D016328:NF-kappa B / Q000235:genetics / Q000276:immunology; D051381:Rats; D012475:Salmonella / Q000276:immunology; D012480:Salmonella Infections / Q000276:immunology / Q000382:microbiology / Q000503:physiopathology; D012772:Shock, Septic / Q000276:immunology* / Q000382:microbiology / Q000503:physiopathology*; D051198:Toll-Like Receptor 5 / Q000235:genetics / Q000276:immunology
chemical_list: D016207:Cytokines; D016328:NF-kappa B; D051198:Toll-Like Receptor 5; D005408:Flagellin