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Inhibition of direct and indirect TLR-mediated activation of human NK cells by low molecular weight dextran sulfate

Millard, Anne-Laure
Spirig, Rolf
Mueller, Nicolas J.
Rieben, Robert
Published in Molecular Immunology. 2010, vol. 47, no. 14, p. 2349-2358
Abstract NK cells express toll-like receptors (TLR) that recognize conserved pathogen or damage associated molecular patterns and play a fundamental role in innate immunity. Low molecular weight dextran sulfate (DXS), known to inhibit the complement system, has recently been reported by us to inhibit TLR4-induced maturation of human monocyte-derived dendritic cells (MoDC). In this study, we investigated the capability of DXS to interfere with human NK cell activation triggered directly by TLR2 agonists or indirectly by supernatants of TLR4-activated MoDC. Both TLR2 agonists and supernatants of TLR4-activated MoDC activated NK cells phenotypically, as demonstrated by the analysis of NK cell activation markers (CD56, CD25, CD69, NKp30, NKp44, NKp46, DNAM-1 and NKG2D), and functionally as shown by increased NK cell degranulation (CD107a surface expression) and IFN-gamma secretion. DXS prevented the up-regulation of NK cell activation markers triggered by TLR2 ligands or supernatants of TLR4-activated MoDC and dose-dependently abrogated NK cell degranulation and IFN-gamma secretion. In summary our results suggest that DXS may be a useful reagent to inhibit the direct and indirect TLR-mediated activation of NK cells.
Keywords Cell Degranulation/drug effectsCell Survival/drug effectsComplement Inactivating Agents/chemistry/pharmacologyCulture Media, ConditionedDendritic Cells/drug effects/immunologyDextran Sulfate/chemistry/*pharmacologyHumansImmunity, Innate/drug effectsInterferon-gamma/biosynthesisKiller Cells, Natural/cytology/*drug effects/*immunologyLymphocyte Activation/drug effects/immunologyMolecular WeightToll-Like Receptor 2/agonists/antagonists & inhibitorsToll-Like Receptor 4/agonists/antagonists & inhibitorsToll-Like Receptors/*antagonists & inhibitors
PMID: 20541808
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Research group Groupe Seebach Jorg Dieter (transplantation et immunologie) (856)
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MILLARD, Anne-Laure et al. Inhibition of direct and indirect TLR-mediated activation of human NK cells by low molecular weight dextran sulfate. In: Molecular Immunology, 2010, vol. 47, n° 14, p. 2349-2358. doi: 10.1016/j.molimm.2010.05.284 https://archive-ouverte.unige.ch/unige:21143

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Deposited on : 2012-05-23

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