Toll-like receptor activation of human cells by synthetic triacylated lipid A-like molecules |
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Authors: | Dunn-Siegrist Irène Tissières Pierre Drifte Geneviève Bauer Jacques Moutel Stéphane Pugin Jérôme |
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Institution: | Intensive Care Laboratory and Department of Microbiology and Molecular Medicine, Faculty of Medicine, University of Geneva, 1211 Geneva 14, Switzerland. |
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Abstract: | Recognition of microbial molecules by mammalian host receptors is essential to mount an immune response. Hexaacylated LPS is the prototypic example of a bacterial molecule recognized by the receptor complex TLR4/MD-2 with its lipid A moiety, whereas bacterial lipopeptides are recognized by TLR2. Here we show that a series of synthetic triacylated lipid A-like molecules are weak Toll-like receptor (TLR) agonists (mainly TLR2 agonists) but very potent TLR4/MD-2 antagonists (submicromolar range). Not only do they block human cell responses to LPS but also to whole gram-negative bacteria, and they inhibit the phagocytosis of gram-negative bacteria. These compounds may represent promising immunomodulatory agents. |
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Keywords: | Lipopolysaccharide (LPS) Lipoprotein Phagocytosis Sepsis Toll-like Receptors (TLR) |
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