Cytokine induction by purified lipoteichoic acids from various bacterial species - Role of LBP, sCD14, CD14 and failure to induce IL-12 and subsequent IFN-γ release

Corinna Hermann, Ingo Spreitzer, Nicolas W.J. Schröder, Siegfried Morath, Martin D. Lehner, Werner Fischer, Christine Schütt, Ralf R. Schumann, Thomas Hartung

Research output: Contribution to journalArticlepeer-review

Abstract

We have recently shown that highly purified lipoteichoic acid (LTA) represents a major immunostimulatory principle of Staphylococcus aureus. In order to test whether this translates to other bacterial species, we extracted and purified LTA from 12 laboratory-grown species. All LTA induced the release of TNF-α, IL-1β, IL-6 and IL-10 in human whole blood. Soluble CD14 (sCD14) inhibited monokine induction by LTA but failed to confer LTA responsiveness for IL-6 and IL-8 release of human umbilical vein endothelial cells (HUVEC). In a competitive LPS-binding protein (LBP) binding assay, the IC50 of the tested LTA preparations was up to 3,230-fold higher than for LPS. LBP enhanced TNF-α release of human peripheral blood mononuclear cells (PBMC) upon LPS but not LTA stimulation. These data demonstrate a differential role for the serum proteins LBP and sCD14 in the recognition of LPS and LTA. Different efficacies of various anti-CD14 antibodies against LPS vs. LTA-induced cytokine release suggest that the recognition sites of CD14 for LPS and LTA are distinct with a partial overlap. While the maximal achievable monokine release in response to LTA was comparable to LPS, all LTA induced significantly less IL-12 and IFN-γ. IL-12 substitution increased LTA-inducible IFN-γ release up to 180-fold, suggesting a critical role of poor LTA-inducible IL-12 for IFN-γ formation. Pretreatment with IFN-γ rendered galactosamine-sensitized mice sensitive to challenge with LTA. In conclusion, LTA compared to LPS, are weak inducers of IL-12 and subsequent IFN-γ formation which might explain their lower toxicity in vivo.

Original languageEnglish (US)
Pages (from-to)541-551
Number of pages11
JournalEuropean Journal of Immunology
Volume32
Issue number2
DOIs
StatePublished - 2002
Externally publishedYes

Keywords

  • Blood
  • Cytokine
  • Lipopolysaccharide
  • Macrophage
  • Monocyte

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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