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

Autor: Rolf Spirig, Nicolas J. Mueller, Anne-Laure Millard, Robert Rieben, Jorg Dieter Seebach
Rok vydání: 2010
Předmět:
Toll-Like Receptors/*antagonists & inhibitors
Cell Survival
Immunology
In Vitro Techniques
Biology
Lymphocyte Activation
Cell Degranulation
Interferon-gamma
Interferon-gamma/biosynthesis
Killer Cells
Natural/cytology/*drug effects/*immunology
Immunity
Innate/drug effects
Humans
Secretion
IL-2 receptor
Receptor
Cell Degranulation/drug effects
Molecular Biology
ddc:616
Toll-like receptor
Innate immune system
Dextran Sulfate
Toll-Like Receptors
Dendritic Cells
NKG2D
Molecular biology
Immunity
Innate
Toll-Like Receptor 2
Dendritic Cells/drug effects/immunology
Complement system
Killer Cells
Natural
Molecular Weight
Toll-Like Receptor 4
TLR2
Complement Inactivating Agents
Culture Media
Conditioned
Toll-Like Receptor 2/agonists/antagonists & inhibitors
Toll-Like Receptor 4/agonists/antagonists & inhibitors
Lymphocyte Activation/drug effects/immunology
Complement Inactivating Agents/chemistry/pharmacology
Cell Survival/drug effects
Dextran Sulfate/chemistry/*pharmacology
Zdroj: Molecular Immunology, Vol. 47, No 14 (2010) pp. 2349-2358
ISSN: 0161-5890
Popis: 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.
Databáze: OpenAIRE
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