Peptidoglycan- and lipoteichoic acid-induced cell activation is mediated by toll-like receptor 2

The Life-threatening complications of sepsis in humans are elicited by infe ction with Gram-negative as well as Gram-positive bacteria. Recently, lipop olysaccharide (LPS), a major biologically active agent of Gram-negative bac teria, was shown to mediate cellular activation by a member of the human To ll-like receptor family, Toll-like receptor (TLR) 2. Here we investigate th e mechanism of cellular activation by soluble peptidoglycan (sPGN) and lipo teichoic acid (LTA), main stimulatory components of Gram-positive bacteria, Like LPS, sPGN and LTA bind to the glycosylphosphatidylinositol-anchored m embrane protein CD14 and induce activation of the transcription factor NF-k appa B in host cells like macrophages. We show that whole Gram-positive bac teria, sPGN and LTA induce the activation of NF-kappa B in HEK293 cells exp ressing TLR2 but not in cells expressing TLR1 or TLR4. The sPGN- and LTA-in duced NF-kappa B activation was not inhibited by polymyxin B, an antibiotic that binds and neutralizes LPS. Coexpression together with membrane CD14 e nhances sPGN signal transmission through TLR2. In contrast to LPS signaling , activation of TLR2 by sPGN and LTA does not require serum. These findings identify TLR2 as a signal transducer for sPGN and LTA in addition to LPS.