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Infection and Immunity, November 2002, p. 6043-6047, Vol. 70, No. 11
0019-9567/02/$04.00+0     DOI: 10.1128/IAI.70.11.6043-6047.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

The Polysaccharide Portion Plays an Indispensable Role in Salmonella Lipopolysaccharide-Induced Activation of NF-{kappa}B through Human Toll-Like Receptor 4

Masashi Muroi and Ken-ichi Tanamoto*

Division of Microbiology, National Institute of Health Sciences, Setagaya, Tokyo 158-8501, Japan

Received 21 March 2002/ Returned for modification 5 June 2002/ Accepted 6 August 2002

The lipid A portion has been identified as the active center responsible for lipopolysaccharide (LPS)-induced macrophage activation. However, we found that Salmonella (Salmonella enterica serovars Abortusequi, Minnesota, and Typhimurium) lipid A is inactive in human macrophages, despite its LPS being highly active. Thus we investigated the critical role of polysaccharide in Salmonella LPS-induced activation of NF-{kappa}B. In human monocytic cell line THP-1, Salmonella lipid A and synthetic Salmonella-type lipid A (516) did not induce NF-{kappa}B-dependent reporter activity up to 1 µg/ml, whereas strong activation was observed in response to Salmonella LPS. The difference in activity between this lipid A and LPS was further examined by using 293 cells expressing human CD14/Toll-like receptor 4 (TLR4)/MD-2, and similar results were obtained in these cells as well. A polysaccharide preparation obtained from Salmonella LPS was inactive in 293 cells expressing human CD14/TLR4/MD-2 even in combination with 516. Salmonella enterica serovar Minnesota Re LPS, whose structure consists of lipid A and two molecules of 2-keto-3-deoxyoctonic acid, but not its lipid A exhibited strong activity in THP-1 cells and 293 cells expressing human CD14/TLR4/MD-2. These results indicate that the polysaccharide portion covalently bound to lipid A plays the principal role in Salmonella LPS-induced activation of NF-{kappa}B through human CD14/TLR4/MD-2.

* Corresponding author. Mailing address: Division of Microbiology, National Institute of Health Sciences, 1-18-1 Kamiyoga, Setagaya, Tokyo 158-8501, Japan. Phone: 81-3-3700-1141, ext. 272. Fax: 81-3-3707-6950. E-mail: tanamoto{at}nihs.go.jp.

Editor: V. J. DiRita

Infection and Immunity, November 2002, p. 6043-6047, Vol. 70, No. 11
0019-9567/02/$04.00+0     DOI: 10.1128/IAI.70.11.6043-6047.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



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