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Infection and Immunity, October 2007, p. 4831-4837, Vol. 75, No. 10
0019-9567/07/$08.00+0     doi:10.1128/IAI.00237-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Bartonella quintana Lipopolysaccharide Is a Natural Antagonist of Toll-Like Receptor 4

Calin Popa,^1,2, Shahla Abdollahi-Roodsaz,^2, Leo A. B. Joosten,^1,2 Nozomi Takahashi,² Tom Sprong,^1,4 Giovanni Matera,³ Maria Carla Liberto,³ Alfredo Foca,³ Marcel van Deuren,^1,4 Bart Jan Kullberg,^1,4 Wim B. van den Berg,² Jos W. M. van der Meer,^1,4 and Mihai G. Netea^1,4*

Department of General Internal Medicine,¹ Rheumatology Research & Advanced Therapeutics, Department of Rheumatology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands,² Institute of Microbiology, Department of Medical Sciences, University of Catanzaro, Catanzaro, Italy,³ Nijmegen University Centre for Infectious Diseases, Nijmegen, The Netherlands⁴

Received 13 February 2007/ Returned for modification 24 March 2007/ Accepted 20 June 2007

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 1ß (IL-1ß), 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.

Published ahead of print on 7 July 2007.

Editor: J. L. Flynn

C.P. and S.A.-R. contributed equally to this study.