MD-2, a novel accessory molecule, is involved in species-specific actions of Salmonella lipid A.
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.
Muroi
Masashi
M
Division of Microbiology, National Institute of Health Sciences, 1-18-1 Kamiyoga, Setagaya, Tokyo 158-8501, Japan.
Ohnishi
Takahiro
T
Tanamoto
Ken-ichi
K
D000818:Animals; D000954:Antigens, Surface / Q000235:genetics / Q000276:immunology*; D002460:Cell Line; D029721:Drosophila Proteins; D015870:Gene Expression; D006801:Humans; D008050:Lipid A / Q000737:chemistry / Q000276:immunology*; D018950:Lipopolysaccharide Receptors / Q000235:genetics / Q000276:immunology*; D051218:Lymphocyte Antigen 96; D008562:Membrane Glycoproteins / Q000235:genetics / Q000276:immunology*; D051379:Mice; D015394:Molecular Structure; D011956:Receptors, Cell Surface / Q000235:genetics / Q000276:immunology*; D019779:Salmonella enterica; D013045:Species Specificity; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors
D000954:Antigens, Surface; D029721:Drosophila Proteins; C495377:LY96 protein, human; D008050:Lipid A; D018950:Lipopolysaccharide Receptors; D051218:Lymphocyte Antigen 96; D008562:Membrane Glycoproteins; D011956:Receptors, Cell Surface; C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors