Human toll-like receptor 2 confers responsiveness to bacterial lipopolysaccharide.
Bacterial lipopolysaccharide (LPS) induces activation of the transcription factor nuclear factor kappaB (NF-kappaB) in host cells upon infection. LPS binds to the glycosylphosphatidylinositol (GPI)- anchored membrane protein CD14, which lacks an intracellular signaling domain. Here we investigated the role of mammalian Toll-like receptors (TLRs) as signal transducers for LPS. Overexpression of TLR2, but not TLR1, TLR4, or CD14 conferred LPS inducibility of NF-kappaB activation in mammalian 293 cells. Mutational analysis demonstrated that this LPS response requires the intracellular domain of TLR2. LPS signaling through TLR2 was dependent on serum which contains soluble CD14 (sCD14). Coexpression of CD14 synergistically enhanced LPS signal transmission through TLR2. In addition, purified recombinant sCD14 could substitute for serum to support LPS-induced TLR2 activation. LPS stimulation of TLR2 initiated an interleukin 1 receptor-like NF-kappaB signaling cascade. These findings suggest that TLR2 may be a signaling component of a cellular receptor for LPS.
Kirschning
C J
CJ
Tularik, Inc., South San Francisco, California 94080, USA.
Wesche
H
H
Merrill Ayres
T
T
Rothe
M
M
D002460:Cell Line; D029721:Drosophila Proteins; D006801:Humans; D007375:Interleukin-1 / Q000378:metabolism; D018950:Lipopolysaccharide Receptors / Q000276:immunology / Q000378:metabolism; D008070:Lipopolysaccharides / Q000276:immunology / Q000378:metabolism* / Q000494:pharmacology; D008562:Membrane Glycoproteins / Q000819:agonists / Q000276:immunology / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000819:agonists / Q000276:immunology / Q000378:metabolism*; D017472:Receptors, Interleukin-1 / Q000276:immunology / Q000378:metabolism; D015398:Signal Transduction / Q000276:immunology; D051194:Toll-Like Receptor 1; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors
D029721:Drosophila Proteins; D007375:Interleukin-1; D018950:Lipopolysaccharide Receptors; D008070:Lipopolysaccharides; D008562:Membrane Glycoproteins; D016328:NF-kappa B; D011956:Receptors, Cell Surface; D017472:Receptors, Interleukin-1; C495342:TLR2 protein, human; C495345:TLR4 protein, human; D051194:Toll-Like Receptor 1; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors