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

Ralf Schwandner, Roman Dziarski, Holger Wesche, Mike Rothe, Carsten J. Kirschning

Research output: Contribution to journalArticle

1331 Citations (Scopus)

Abstract

The life-threatening complications of sepsis in humans are elicited by infection with Gram-negative as well as Gram-positive bacteria. Recently, lipopolysaccharide (LPS), a major biologically active agent of Gram-negative bacteria, was shown to mediate cellular activation by a member of the human Toll-like receptor family, Toll-like receptor (TLR) 2. Here we investigate the mechanism of cellular activation by soluble peptidoglycan (sPGN) and lipoteichoic acid (LTA), main stimulatory components of Gram-positive bacteria. Like LPS, sPGN and LTA bind to the glycosylphosphatidylinositol- anchored membrane protein CD14 and induce activation of the transcription factor NF-κB in host cells like macrophages. We show that whole Gram- positive bacteria, sPGN and LTA induce the activation of NF-κB in HEK293 cells expressing TLR2 but not in cells expressing TLR1 or TLR4. The sPGN- and LTA-induced NF-κB activation was not inhibited by polymyxin B, an antibiotic that binds and neutralizes LPS. Coexpression together with membrane CD14 enhances 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.

Original languageEnglish
Pages (from-to)17406-17409
Number of pages4
JournalJournal of Biological Chemistry
Volume274
Issue number25
DOIs
StatePublished - Jun 18 1999

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Toll-Like Receptor 2
Peptidoglycan
Chemical activation
Lipopolysaccharides
Bacteria
Gram-Positive Bacteria
Cells
Polymyxin B
Glycosylphosphatidylinositols
Macrophages
HEK293 Cells
Toll-Like Receptors
lipoteichoic acid
Gram-Negative Bacteria
Transducers
Sepsis
Membrane Proteins
Transcription Factors
Anti-Bacterial Agents
Membranes

ASJC Scopus subject areas

  • Biochemistry

Cite this

Peptidoglycan- and lipoteichoic acid-induced cell activation is mediated by Toll-like receptor 2. / Schwandner, Ralf; Dziarski, Roman; Wesche, Holger; Rothe, Mike; Kirschning, Carsten J.

In: Journal of Biological Chemistry, Vol. 274, No. 25, 18.06.1999, p. 17406-17409.

Research output: Contribution to journalArticle

Schwandner, Ralf ; Dziarski, Roman ; Wesche, Holger ; Rothe, Mike ; Kirschning, Carsten J. / Peptidoglycan- and lipoteichoic acid-induced cell activation is mediated by Toll-like receptor 2. In: Journal of Biological Chemistry. 1999 ; Vol. 274, No. 25. pp. 17406-17409.
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