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Infection and Immunity, July 2002, p. 3546-3550, Vol. 70, No. 7
0019-9567/02/$04.00+0     DOI: 10.1128/IAI.70.7.3546-3550.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

MD-2, a Novel Accessory Molecule, Is Involved in Species-Specific Actions of Salmonella Lipid A

Masashi Muroi, Takahiro Ohnishi, and Ken-ichi Tanamoto*

Division of Microbiology, National Institute of Health Sciences, 1-18-1 Kamiyoga, Setagaya, Tokyo 158-8501, Japan

Received 3 December 2001/ Returned for modification 6 February 2002/ Accepted 27 March 2002

Salmonella lipid A is inactive in human macrophages despite being potently active in murine macrophages. We investigated the molecular basis for this species-specific action of Salmonella lipid A. When murine CD14 (mCD14), mTLR4, and mMD-2 were all expressed in human monocytic THP-1 cells, these cells were capable of responding to Salmonella lipid A. Expressing each of these proteins separately did not impart such responsiveness. Expression of mTLR4 plus mMD-2, but not mCD14 plus mTLR4 or mCD14 plus mMD-2, conferred this responsiveness. In THP-1 cells expressing mCD14, mTLR4, and mMD-2, replacing mCD14 with human CD14 had no effect on responsiveness to Salmonella lipid A or synthetic Salmonella-type lipid A (compound 516). When mTLR4 was replaced with human TLR4, the responses to these lipid A preparations were decreased to half, and the replacement of mMD-2 decreased responsiveness to one-third, although the responses to Escherichia coli lipid A or synthetic E. coli-type lipid A (compound 506) were not affected. These results indicate that both TLR4 and MD-2 participate in the species-specific action of Salmonella lipid A.


* 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: A. D. O'Brien


Infection and Immunity, July 2002, p. 3546-3550, Vol. 70, No. 7
0019-9567/02/$04.00+0     DOI: 10.1128/IAI.70.7.3546-3550.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.




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