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Toll-like receptor activation of human cells by synthetic triacylated lipid A-like molecules

Bauer, Jacques
Moutel, Stéphane
Published in The Journal of biological chemistry. 2012, vol. 287, no. 20, p. 16121-31
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.
Keywords Gram-Negative Bacteria/immunology/metabolismHEK293 CellsHumansImmunologic Factors/chemical synthesis/immunology/pharmacologyLipid A/chemical synthesis/immunology/pharmacologyLymphocyte Antigen 96/immunology/metabolismToll-Like Receptor 2/agonists/antagonists & inhibitors/immunology/metabolismToll-Like Receptor 4/agonists/antagonists & inhibitors/immunology/metabolism
PMID: 22433865
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Research group Groupe Pugin Jérôme (Soins intensifs) (587)
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DUNN-SIEGRIST, Irène et al. Toll-like receptor activation of human cells by synthetic triacylated lipid A-like molecules. In: Journal of Biological Chemistry, 2012, vol. 287, n° 20, p. 16121-31. doi: 10.1074/jbc.M112.348383 https://archive-ouverte.unige.ch/unige:32317

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Deposited on : 2013-12-17

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