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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 and von Aulock, Sonja 2010. Internalization and coreceptor expression are critical for TLR2-mediated recognition of lipoteichoic acid in human peripheral blood. The Journal of Immunology 185 (6) , pp. 3708-3717. 10.4049/jimmunol.0901660

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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.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
Subjects: R Medicine > RZ Other systems of medicine
Publisher: American Association of Immunologists
ISSN: 0022-1767
Last Modified: 04 Jun 2017 03:41

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