title: Acinetobacter baumannii lipopolysaccharides are potent stimulators of human monocyte activation via Toll-like receptor 4 signalling.
abstract: Acinetobacter baumannii is a major nosocomial pathogen and frequent cause of hospital-acquired pneumonia, surgical wound infections and sepsis. As very little is known of the endotoxic potential of A. baumannii lipopolysaccharide (LPS) with respect to human cells or of its ability to stimulate inflammatory signalling via human Toll-like receptors (TLRs), the biological activity of these endotoxins was investigated in human monocytic THP-1 cells and in TLR-deficient HEK-293 cells transfected with human TLR2 and TLR4 constructs. Endotoxins derived from five clinical isolates of A. baumannii and one of Acinetobacter 'genomospecies 9' showed high potency, which was comparable to that of Escherichia coli strain R1 NCTC 13114 LPS, in the induction of the Limulus amoebocyte reaction and interleukin 8 and tumour necrosis factor alpha release from THP-1 cells. Whole UV-killed cells of A. baumannii and Acinetobacter 'genomospecies 9' stimulated both TLR2- and TLR4-dependent signalling, whereas pure endotoxins of all investigated strains induced signalling via TLR4, but not TLR2.
authors.affiliation: Department of Bioscience, 204 George Street, University of Strathclyde, Glasgow G1 1XW, UK.
authors.forename: Clett
authors.initials: C
authors.lastname: Erridge
authors.affiliation: Medical Microbiology, Centre for Infectious Diseases, University of Edinburgh College of Medicine and Veterinary Medicine, Chancellor's Building, 49 Little France Crescent, Edinburgh EH16 4SB, UK.
authors.forename: Olga L
authors.initials: OL
authors.lastname: Moncayo-Nieto
authors.affiliation: Medical Microbiology, Centre for Infectious Diseases, University of Edinburgh College of Medicine and Veterinary Medicine, Chancellor's Building, 49 Little France Crescent, Edinburgh EH16 4SB, UK.
authors.forename: Robert
authors.initials: R
authors.lastname: Morgan
authors.affiliation: Medical Microbiology, Centre for Infectious Diseases, University of Edinburgh College of Medicine and Veterinary Medicine, Chancellor's Building, 49 Little France Crescent, Edinburgh EH16 4SB, UK.
authors.forename: Michelle
authors.initials: M
authors.lastname: Young
authors.affiliation: Medical Microbiology, Centre for Infectious Diseases, University of Edinburgh College of Medicine and Veterinary Medicine, Chancellor's Building, 49 Little France Crescent, Edinburgh EH16 4SB, UK.
authors.forename: Ian R
authors.initials: IR
authors.lastname: Poxton
mesh_terms: D040981:Acinetobacter baumannii / Q000276:immunology*; D004926:Escherichia coli / Q000276:immunology; D006801:Humans; D016209:Interleukin-8 / Q000096:biosynthesis; D008070:Lipopolysaccharides / Q000276:immunology*; D009000:Monocytes / Q000276:immunology*; D015398:Signal Transduction; D051195:Toll-Like Receptor 2 / Q000172:deficiency / Q000276:immunology; D051197:Toll-Like Receptor 4 / Q000172:deficiency / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
chemical_list: D016209:Interleukin-8; D008070:Lipopolysaccharides; C495345:TLR4 protein, human; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D014409:Tumor Necrosis Factor-alpha