Human Toll-like receptor 2 confers responsiveness to bacterial lipopolysaccharide

Bacterial lipopolysaccharide (LPS) induces activation of the transcription factor nuclear factor kappa B (NF-kappa B) in host cells upon infection. LP S binds to the glycosylphosphatidylinositol (GPI)anchored membrane protein CD14, which lacks an intracellular signaling domain. Here we investigated t he role of mammalian Toll-like receptors (TLRs) as signal transducers for L PS. Overexpression of TLR2, but not TLR1, TLR4, or CD14 conferred LPS induc ibility of NF-kappa B activation in mammalian 293 cells. Mutational analysi s demonstrated that this LPS response requires the intracellular domain of TLR2. LPS signaling through TLR2 was dependent on serum which contains solu ble CD14 (sCD14). Coexpression of CD14 synergistically enhanced LPS signal transmission through TLR2, In addition, purified recombinant sCD14 could su bstitute for serum to support LPS-induced TLR2 activation. LPS stimulation of TLR2 initiated an interleukin 1 receptor-like NF-kappa B signaling casca de. These findings suggest that TLR2 may be a signaling component of a cell ular receptor for LPS.