Lipopolysaccharide recognition: CD14, TLRs and the LPS-activation cluster.
Recognition of bacterial lipopolysaccharide (LPS) by the innate immune system elicits strong pro-inflammatory responses that can eventually cause a fatal sepsis syndrome in humans. LPS-mediated activation of mammalian cells is believed to involve the interaction of LPS with lipopolysaccharide-binding protein (LBP) in the serum and, subsequently with CD14. Although there is no doubt that CD14 binds LPS, CD14 is not capable of initiating a transmembrane activation signal because it is a glycosylphosphatidylinositol (GPI)-anchored protein. Accumulating evidence has suggested that LPS must interact with a transmembrane receptor(s) that is responsible for signal transduction. Integrins CD11c and/or CD18, Toll-like receptors (TLRs), as well as CD55, have been suggested to serve this function. Recently, we have revealed that a signalling complex of receptors is formed following LPS stimulation, which comprises heat-shock proteins (Hsps) 70 and 90, chemokine receptor 4 (CXCR4) and growth differentiation factor 5 (GDF5). Taking into account the discovery of the TLRs and the LPS-activation cluster, we propose a new model of LPS recognition.
Triantafilou
Martha
M
Institute of Biomedical and Biomolecular Sciences, School of Biological Sciences, University of Portsmouth, King Henry Building, King Henry I Street, PO1 2DY, Portsmouth, UK.
Triantafilou
Kathy
K
D000818:Animals; D019485:Bone Morphogenetic Proteins; D029721:Drosophila Proteins; D017261:Glycosylphosphatidylinositols / Q000378:metabolism; D055428:Growth Differentiation Factor 5; D006133:Growth Substances / Q000378:metabolism; D006360:Heat-Shock Proteins / Q000378:metabolism; D007113:Immunity, Innate; D018950:Lipopolysaccharide Receptors / Q000276:immunology*; D008070:Lipopolysaccharides / Q000276:immunology* / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000187:drug effects*; D046911:Macromolecular Substances; D008562:Membrane Glycoproteins / Q000276:immunology*; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018448:Models, Immunological; D019718:Receptors, CXCR4 / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000276:immunology*; D051193:Toll-Like Receptors
D019485:Bone Morphogenetic Proteins; D029721:Drosophila Proteins; C525893:GDF5 protein, human; C525894:Gdf5 protein, mouse; D017261:Glycosylphosphatidylinositols; D055428:Growth Differentiation Factor 5; D006133:Growth Substances; D006360:Heat-Shock Proteins; D018950:Lipopolysaccharide Receptors; D008070:Lipopolysaccharides; D046911:Macromolecular Substances; D008562:Membrane Glycoproteins; D019718:Receptors, CXCR4; D011956:Receptors, Cell Surface; D051193:Toll-Like Receptors