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

Research output: Contribution to journalArticle

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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Blood Cells
Lipoproteins
lipoteichoic acid
Kidney
Gram-Positive Bacteria
Cellular Structures
Immobilization
Cell Wall
Staphylococcus aureus
Immunoglobulin G
Cytokines
Serum

ASJC Scopus subject areas

  • Immunology

Cite this

Bunk, S., Sigel, S., Metzdorf, D., Sharif, O., Triantafilou, K., Triantafilou, M., ... 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

Internalization and coreceptor expression are critical for TLR2-mediated recognition of lipoteichoic acid in human peripheral blood. / Bunk, Sebastian; Sigel, Stefanie; Metzdorf, Daniela; Sharif, Omar; Triantafilou, Kathy; Triantafilou, Martha; Hartung, Thomas; Knapp, Sylvia; Von Aulock, Sonja.

In: Journal of Immunology, Vol. 185, No. 6, 15.09.2010, p. 3708-3717.

Research output: Contribution to journalArticle

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, vol. 185, no. 6, pp. 3708-3717. https://doi.org/10.4049/jimmunol.0901660
Bunk, Sebastian ; Sigel, Stefanie ; Metzdorf, Daniela ; Sharif, Omar ; Triantafilou, Kathy ; Triantafilou, Martha ; Hartung, Thomas ; Knapp, Sylvia ; Von Aulock, Sonja. / Internalization and coreceptor expression are critical for TLR2-mediated recognition of lipoteichoic acid in human peripheral blood. In: Journal of Immunology. 2010 ; Vol. 185, No. 6. pp. 3708-3717.
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AU - Sharif, Omar

AU - Triantafilou, Kathy

AU - Triantafilou, Martha

AU - Hartung, Thomas

AU - Knapp, Sylvia

AU - Von Aulock, Sonja

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