Lipopolysaccharide recognition: CD14, TLRs and the LPS-activation cluster

Trends Immunol. 2002 Jun;23(6):301-4. doi: 10.1016/s1471-4906(02)02233-0.


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.

Publication types

  • Review

MeSH terms

  • Animals
  • Bone Morphogenetic Proteins*
  • Drosophila Proteins*
  • Glycosylphosphatidylinositols / metabolism
  • Growth Differentiation Factor 5
  • Growth Substances / metabolism
  • Heat-Shock Proteins / metabolism
  • Immunity, Innate
  • Lipopolysaccharide Receptors / immunology*
  • Lipopolysaccharides / immunology*
  • Lipopolysaccharides / pharmacology
  • Lymphocyte Activation / drug effects*
  • Macromolecular Substances
  • Membrane Glycoproteins / immunology*
  • Mice
  • Mice, Inbred C3H
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Models, Immunological
  • Receptors, CXCR4 / metabolism
  • Receptors, Cell Surface / immunology*
  • Toll-Like Receptors


  • Bone Morphogenetic Proteins
  • Drosophila Proteins
  • GDF5 protein, human
  • Gdf5 protein, mouse
  • Glycosylphosphatidylinositols
  • Growth Differentiation Factor 5
  • Growth Substances
  • Heat-Shock Proteins
  • Lipopolysaccharide Receptors
  • Lipopolysaccharides
  • Macromolecular Substances
  • Membrane Glycoproteins
  • Receptors, CXCR4
  • Receptors, Cell Surface
  • Toll-Like Receptors