Bartonella quintana lipopolysaccharide is a natural antagonist of Toll-like receptor 4.
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.
Popa
Calin
C
Department of General Internal Medicine, Radboud University Nijmegen Medical Centre, The Netherlands.
Abdollahi-Roodsaz
Shahla
S
Joosten
Leo A B
LA
Takahashi
Nozomi
N
Sprong
Tom
T
Matera
Giovanni
G
Liberto
Maria Carla
MC
Foca
Alfredo
A
van Deuren
Marcel
M
Kullberg
Bart Jan
BJ
van den Berg
Wim B
WB
van der Meer
Jos W M
JW
Netea
Mihai G
MG
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
D053583:Interleukin-1beta; D008070:Lipopolysaccharides; D051197:Toll-Like Receptor 4; D014409:Tumor Necrosis Factor-alpha; D000093242:Interleukin-6 Inhibitors