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J Biol Chem. 2012 May 11;287(20):16121-31. doi: 10.1074/jbc.M112.348383. Epub 2012 Mar 20.

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

Author information

1
Intensive Care Laboratory and Department of Microbiology and Molecular Medicine, Faculty of Medicine, University of Geneva, 1211 Geneva 14, Switzerland.

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.

PMID:
22433865
PMCID:
PMC3351317
DOI:
10.1074/jbc.M112.348383
[Indexed for MEDLINE]
Free PMC Article
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