International Immunology, Vol. 13, No. 12, 1595-1599,
December 2001
© 2001 Japanese Society for Immunology
Human MD-2 confers on mouse Toll-like receptor 4 species-specific lipopolysaccharide recognition
Departments of Immunology and
1 Internal Medicine, Saga Medical School, 5-1-1 Nabeshima, Saga 849-8501, Japan
2 Department of Chemistry, Graduate School of Science, Osaka University, Osaka 560-0043, Japan
3 Department of Biochemistry and Cell Biology, National Institute of Infectious Diseases, Tokyo 162-8640, Japan
Correspondence to: K. Miyake, Division of Infectious Genetics, Department of Microbiology and Immunology, Institute of Medical Science, University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan
Toll-like receptor 4 (TLR4) recognizes lipopolysaccharide (LPS). MD-2 is associated with TLR4 and imparts LPS responsiveness to it. Little is known, however, as to whether MD-2 directly regulates LPS recognition by TLR4. To address the issue, we took advantage of a species-specific pharmacology of lipid IVa, an analogue of lipid A. Lipid IVa acted agonistically on mouse (m) TLR4/MD-2 but not on human (h) TLR4/MD-2. Lipid IVa antagonized the agonistic effect of lipid A on hTLR4/MD-2. We examined the chimeric complex consisting of mTLR4 and hMD-2 to ask whether species specificity is conferred by TLR4 or MD-2. hMD-2 was clearly distinct from mMD-2 in the way of influencing LPS recognition by mTLR4. hMD-2 conferred on mTLR4 responsiveness to lipid A but not to lipid IVa. Moreover, lipid IVa acted as a lipid A antagonist on mTLR4 that is associated with hMD-2. Collectively, MD-2 directly influences the fine specificity of TLR4.
Keywords: innate immunity, MD-2, TLR4
Transmitting editor: T. Kurosaki
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