HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Royle, M. C. J. Articles by Bryant, C. E. Search for Related Content PubMed PubMed Citation Articles by Royle, M. C. J. Articles by Bryant, C. E.

Stimulation of Toll-Like Receptor 4 by Lipopolysaccharide During Cellular Invasion by Live Salmonella typhimurium Is a Critical But Not Exclusive Event Leading to Macrophage Responses¹

Department of Clinical Veterinary Medicine, University of Cambridge, Cambridge, United Kingdom

Invasion of macrophages by salmonellae induces cellular responses, with the bacterial inducers likely to include a number of pathogen-associated molecular patterns. LPS is one of the prime candidates, but its precise role in the process, especially when presented as a component of live infecting bacteria, is unclear. We thus investigated this question using the lipid A antagonist E5531, the macrophage-like cell line RAW 264.7, and primary macrophage cultures from C3H/HeJ and Toll-like receptor 4^-/- (TLR-4^-/-) mice. We show that LPS presented on live salmonellae provides an essential signal, via functional TLR-4, for macrophages to produce NO and TNF-. Furthermore, the mitogen-activated protein kinase c-Jun N-terminal kinase and p38 are activated, and the transcription factor NF-B is translocated to the nucleus when RAW 264.7 cells are presented with purified LPS or live salmonellae. Purified LPS stimulates rapid, transitory mitogen-activated protein kinase activation that is inhibited by E5531, whereas bacterial invasion stimulates delayed, prolonged activation, unaffected by E5531. Both purified LPS and bacterial invasion caused translocation of NF-B, but whereas E5531 always inhibited activation by purified LPS, activation by bacterial invasion was only inhibited at later time points. In conclusion, we show for the first time that production of NO and TNF- is critically dependent on activation of TLR-4 by LPS during invasion of macrophages by salmonellae, but that different patterns of activation of intracellular signaling pathways are induced by purified LPS vs live salmonellae.

This article has been cited by other articles:

				M.-F. Roy, N. Riendeau, C. Bedard, P. Helie, G. Min-Oo, K. Turcotte, P. Gros, F. Canonne-Hergaux, and D. Malo Pyruvate kinase deficiency confers susceptibility to Salmonella typhimurium infection in mice J. Exp. Med., November 26, 2007; 204(12): 2949 - 2961. [Abstract] [Full Text] [PDF]

				A. J. Tonks, E. Dudley, N. G. Porter, J. Parton, J. Brazier, E. L. Smith, and A. Tonks A 5.8-kDa component of manuka honey stimulates immune cells via TLR4 J. Leukoc. Biol., November 1, 2007; 82(5): 1147 - 1155. [Abstract] [Full Text] [PDF]

				M. T. Bailey, H. Engler, N. D. Powell, D. A. Padgett, and J. F. Sheridan Repeated social defeat increases the bactericidal activity of splenic macrophages through a Toll-like receptor-dependent pathway Am J Physiol Regulatory Integrative Comp Physiol, September 1, 2007; 293(3): R1180 - R1190. [Abstract] [Full Text] [PDF]

				S. Totemeyer, M. Sheppard, A. Lloyd, D. Roper, C. Dowson, D. Underhill, P. Murray, D. Maskell, and C. Bryant IFN-{gamma} Enhances Production of Nitric Oxide from Macrophages via a Mechanism That Depends on Nucleotide Oligomerization Domain-2. J. Immunol., April 15, 2006; 176(8): 4804 - 4810. [Abstract] [Full Text] [PDF]

				F. S. Laroux, X. Romero, L. Wetzler, P. Engel, and C. Terhorst Cutting Edge: MyD88 Controls Phagocyte NADPH Oxidase Function and Killing of Gram-Negative Bacteria J. Immunol., November 1, 2005; 175(9): 5596 - 5600. [Abstract] [Full Text] [PDF]

				R. W. DePaolo, R. Lathan, B. J. Rollins, and W. J. Karpus The Chemokine CCL2 Is Required for Control of Murine Gastric Salmonella enterica Infection Infect. Immun., October 1, 2005; 73(10): 6514 - 6522. [Abstract] [Full Text] [PDF]

				D. S. Weiss, K. Takeda, S. Akira, A. Zychlinsky, and E. Moreno MyD88, but Not Toll-Like Receptors 4 and 2, Is Required for Efficient Clearance of Brucella abortus Infect. Immun., August 1, 2005; 73(8): 5137 - 5143. [Abstract] [Full Text] [PDF]

				K. Kawasaki, R. K. Ernst, and S. I. Miller Inhibition of Salmonella enterica Serovar Typhimurium Lipopolysaccharide Deacylation by Aminoarabinose Membrane Modification J. Bacteriol., April 1, 2005; 187(7): 2448 - 2457. [Abstract] [Full Text] [PDF]

				S. Totemeyer, P. Kaiser, D. J. Maskell, and C. E. Bryant Sublethal Infection of C57BL/6 Mice with Salmonella enterica Serovar Typhimurium Leads to an Increase in Levels of Toll-Like Receptor 1 (TLR1), TLR2, and TLR9 mRNA as Well as a Decrease in Levels of TLR6 mRNA in Infected Organs Infect. Immun., March 1, 2005; 73(3): 1873 - 1878. [Abstract] [Full Text] [PDF]

				A. Vazquez-Torres, B. A. Vallance, M. A. Bergman, B. B. Finlay, B. T. Cookson, J. Jones-Carson, and F. C. Fang Toll-Like Receptor 4 Dependence of Innate and Adaptive Immunity to Salmonella: Importance of the Kupffer Cell Network J. Immunol., May 15, 2004; 172(10): 6202 - 6208. [Abstract] [Full Text] [PDF]