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

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 (C) 2010 Elsevier Ltd All rights reserved