Identification of bacterial muramyl dipeptide as activator of the NALP3/cryopyrin inflammasome.

Détails

ID Serval
serval:BIB_F144620AF94D
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Identification of bacterial muramyl dipeptide as activator of the NALP3/cryopyrin inflammasome.
Périodique
Current Biology
Auteur(s)
Martinon F., Agostini L., Meylan E., Tschopp J.
ISSN
0960-9822 (Print)
ISSN-L
0960-9822
Statut éditorial
Publié
Date de publication
2004
Volume
14
Numéro
21
Pages
1929-1934
Langue
anglais
Résumé
Activation of caspase-1 and subsequent processing and secretion of the pro-inflammatory cytokine IL-1beta is triggered upon assembly of the inflammasome complex. It is generally believed that bacterial lipopolysaccharides (LPS) are activators of the inflammasome through stimulation of Toll-like receptor 4 (TLR4). Like TLRs, NALP3/Cryopyrin, which is a key component of the inflammasome, contains Leucine-Rich-Repeats (LRRs). LRRs are frequently used to sense bacterial components, thus raising the possibility that bacteria directly activate the inflammasome. Here, we show that bacterial peptidoglycans (PGN), but surprisingly not LPS, induce NALP3-mediated activation of caspase-1 and maturation of proIL-1beta. Activation is independent of TLRs because the PGN degradation product muramyl dipeptide (MDP), which is not sensed by TLRs, is the minimal-activating structure. Macrophages from a patient with Muckle-Wells syndrome, an autoinflammatory disease associated with mutations in the NALP3/Cryopyrin gene, show increased IL-1beta secretion in the presence of MDP. The activation of the NALP3-inflammasome by MDP may be the basis of the potent adjuvant activity of MDP.
Mots-clé
Acetylmuramyl-Alanyl-Isoglutamine/metabolism, Amyloidosis/metabolism, Autoimmunity/immunology, Carrier Proteins/metabolism, Caspase 1/metabolism, Cells, Cultured, Chromatography, Gel, Humans, Inflammation/immunology, Inflammation/metabolism, Interleukin-1/metabolism, Macrophages/metabolism, Peptidoglycan/metabolism, Plasmids/genetics, Syndrome, Urticaria/metabolism
Pubmed
Web of science
Open Access
Oui
Création de la notice
24/01/2008 16:19
Dernière modification de la notice
09/05/2019 3:18
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