Definition of structural prerequisites for lipoteichoic acid-inducible cytokine induction by synthetic derivatives

Susanne Deininger, Andreas Stadelmaier, Sonja Von Aulock, Siegfried Morath, Richard R. Schmidt, Thomas Hartung

Research output: Contribution to journalArticlepeer-review

Abstract

The controversy about the immune stimulatory properties of lipoteichoic acid (LTA) from Staphylococcus aureus was solved recently by showing decomposition and inactivation of LTA obtained by conventional purification strategies, as well as pronounced LPS contamination of commercial preparations. By introducing a novel preparation method, the structure of bioactive LTA was elucidated. This structure was confirmed by chemical synthesis. In this work, synthetic LTA derivatives were employed to study the structure-function relationship of cytokine induction in human monocytes. Synthetic LTA induced the same cytokine pattern as highly purified natural LTA. The gentiobiose core could be omitted without affecting bioactivity. The polyglycerophosphate backbone amplified the response to the lipid anchor (∼100-fold) only when substituted with D-alanine, whereas α-DN-acetylglucosamine substituents could be omitted. Replacing D-alanine substituents with L-alanine reduced the activity of the molecule at least 10-fold, indicating stereoselectivity. These results define for the first time the crucial patterns required for the immune recognition of LTA.

Original languageEnglish (US)
Pages (from-to)4134-4138
Number of pages5
JournalJournal of Immunology
Volume170
Issue number8
DOIs
StatePublished - Apr 15 2003
Externally publishedYes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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