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Title

Toll-like receptor activation of human cells by synthetic triacylated lipid A-like molecules
Authors
Dunn-Siegrist, Irène
Tissières, Pierre
Drifte Roduit, Geneviève Sophie
Bauer, Jacques
Moutel, Stéphane
Pugin, Jérôme
Published in 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/metabolism — HEK293 Cells — Humans — Immunologic Factors/chemical synthesis/immunology/pharmacology — Lipid A/chemical synthesis/immunology/pharmacology — Lymphocyte Antigen 96/immunology/metabolism — Toll-Like Receptor 2/agonists/antagonists & inhibitors/immunology/metabolism — Toll-Like Receptor 4/agonists/antagonists & inhibitors/immunology/metabolism
Identifiers
PMID: 22433865
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Article (Published version) (1.9 MB) - public document Free access
Structures
Faculté de médecine / Section de médecine clinique / Département d'anesthésiologie, pharmacologie et soins intensifs
Faculté de médecine / Section de médecine fondamentale / Département de microbiologie et médecine moléculaire
Research group Groupe Pugin Jérôme (Soins intensifs) (587)
Citation
(ISO format) 		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. https://archive-ouverte.unige.ch/unige:32317

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Deposited on : 2013-12-17

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