title: Bartonella quintana lipopolysaccharide is a natural antagonist of Toll-like receptor 4.
abstract: Bartonella quintana is a gram-negative microorganism that causes trench fever and chronic bacteremia. B. quintana lipopolysaccharide (LPS) was unable to induce the production of proinflammatory cytokines in human monocytes. Interestingly, B. quintana LPS is a potent antagonist of Toll-like receptor 4 (TLR4), as it inhibited both mRNA transcription and the release of tumor necrosis factor alpha, interleukin 1beta (IL-1beta), and IL-6 by Escherichia coli LPS in human monocytes, at ratios ranging from 1,000:1 to 10:1 (B. quintana LPS to E. coli LPS). Likewise, B. quintana LPS blocked the interaction of E. coli LPS with TLR4 in transfected cell lines. The extent of the inhibitory effect of B. quintana LPS was demonstrated in microarray studies, which showed downregulation of practically all genes induced by LPS in monocytes. Because of the role of TLR4 in inflammation, B. quintana LPS may prove useful as a potent anti-TLR4 agent with therapeutic potential in both infections and autoimmune inflammation.
authors.affiliation: Department of General Internal Medicine, Radboud University Nijmegen Medical Centre, The Netherlands.
authors.forename: Calin
authors.initials: C
authors.lastname: Popa
authors.forename: Shahla
authors.initials: S
authors.lastname: Abdollahi-Roodsaz
authors.forename: Leo A B
authors.initials: LA
authors.lastname: Joosten
authors.forename: Nozomi
authors.initials: N
authors.lastname: Takahashi
authors.forename: Tom
authors.initials: T
authors.lastname: Sprong
authors.forename: Giovanni
authors.initials: G
authors.lastname: Matera
authors.forename: Maria Carla
authors.initials: MC
authors.lastname: Liberto
authors.forename: Alfredo
authors.initials: A
authors.lastname: Foca
authors.forename: Marcel
authors.initials: M
authors.lastname: van Deuren
authors.forename: Bart Jan
authors.initials: BJ
authors.lastname: Kullberg
authors.forename: Wim B
authors.initials: WB
authors.lastname: van den Berg
authors.forename: Jos W M
authors.initials: JW
authors.lastname: van der Meer
authors.forename: Mihai G
authors.initials: MG
authors.lastname: Netea
mesh_terms: D018413:Bartonella quintana / Q000737:chemistry* / Q000276:immunology*; D002478:Cells, Cultured; D015536:Down-Regulation; D015964:Gene Expression Regulation, Bacterial; D006801:Humans; D053583:Interleukin-1beta / Q000037:antagonists & inhibitors; D008070:Lipopolysaccharides / Q000276:immunology*; D009000:Monocytes / Q000276:immunology; D020411:Oligonucleotide Array Sequence Analysis; D051197:Toll-Like Receptor 4 / Q000037:antagonists & inhibitors*; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000235:genetics; D000093242:Interleukin-6 Inhibitors
chemical_list: D053583:Interleukin-1beta; D008070:Lipopolysaccharides; D051197:Toll-Like Receptor 4; D014409:Tumor Necrosis Factor-alpha; D000093242:Interleukin-6 Inhibitors