Internalization and coreceptor expression are critical for TLR2-mediated recognition of lipoteichoic acid in human peripheral blood

Sebastian Bunk, Stefanie Sigel, Daniela Metzdorf, Omar Sharif, Kathy Triantafilou, Martha Triantafilou, Thomas Hartung, Sylvia Knapp, Sonja Von Aulock

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Abstract

Lipoteichoic acid (LTA), a ubiquitous cell wall component of Gram-positive bacteria, represents a potent immunostimulatory molecule. Because LTA of a mutant Staphylococcus aureus strain lacking lipoproteins (Δlgt-LTA) has been described to be immunobiologically inactive despite a lack of ascertained structural differences to wild-type LTA (wt-LTA), we investigated the functional requirements for the recognition of Δlgt-LTA by human peripheral blood cells. In this study, we demonstrate that Δlgt-LTA-induced immune activation critically depends on the immobilization of LTA and the presence of human serum components, which, to a lesser degree, was also observed for wt-LTA. Under experimental conditions allowing LTA-mediated stimulation, we found no differences between the immunostimulatory capacity of Δlgt-LTA and wt-LTA in human blood cells, arguing for a limited contribution of possible lipoprotein contaminants to wt-LTA-mediated immune activation. In contrast to human blood cells, TLR2-transfected human embryonic kidney 293 cells could be activated only by wt-LTA, whereas activation of these cells by Δlgt-LTA required the additional expression of TLR6 and CD14, suggesting that activation of human embryonic kidney 293 cells expressing solely TLR2 is probably mediated by residual lipoproteins in wt-LTA. Notably, in human peripheral blood, LTA-specific IgG Abs are essential for Δlgt-LTA-mediated immune activation and appear to induce the phagocytic uptake of Δlgt-LTA via engagement of FcγRII. In this study, we have elucidated a novel mechanism of LTA-induced cytokine induction in human peripheral blood cells that involves uptake of LTA and subsequent intracellular recognition driven by TLR2, TLR6, and CD14.

Original languageEnglish (US)
Pages (from-to)3708-3717
Number of pages10
JournalJournal of Immunology
Volume185
Issue number6
DOIs
StatePublished - Sep 15 2010

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ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Bunk, S., Sigel, S., Metzdorf, D., Sharif, O., Triantafilou, K., Triantafilou, M., Hartung, T., Knapp, S., & Von Aulock, S. (2010). Internalization and coreceptor expression are critical for TLR2-mediated recognition of lipoteichoic acid in human peripheral blood. Journal of Immunology, 185(6), 3708-3717. https://doi.org/10.4049/jimmunol.0901660