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; Seebach, Jörg D; Rieben, Robert (2010). Inhibition of direct and indirect TLR-mediated activation of human NK cells by low molecular weight dextran sulfate. Molecular immunology, 47(14), pp. 2349-58. Amsterdam: Elsevier 10.1016/j.molimm.2010.05.284

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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.

Item Type:	Journal Article (Original Article)
Division/Institute:	04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > Forschungsbereich Mu50 > Forschungsgruppe Herz und Gefässe 04 Faculty of Medicine > Department of Cardiovascular Disorders (DHGE) > Clinic of Heart Surgery
UniBE Contributor:	Spirig, Rolf, Müller, Nicole (A), Rieben, Robert
ISSN:	0161-5890
Publisher:	Elsevier
Language:	English
Submitter:	Factscience Import
Date Deposited:	04 Oct 2013 14:10
Last Modified:	27 Feb 2024 14:29
Publisher DOI:	10.1016/j.molimm.2010.05.284
PubMed ID:	20541808
Web of Science ID:	000284304700007
URI:	https://boris.unibe.ch/id/eprint/1302 (FactScience: 202659)