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

Details

Serval ID
serval:BIB_F144620AF94D
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Identification of bacterial muramyl dipeptide as activator of the NALP3/cryopyrin inflammasome.
Journal
Current Biology
Author(s)
Martinon F., Agostini L., Meylan E., Tschopp J.
ISSN
0960-9822 (Print)
ISSN-L
0960-9822
Publication state
Published
Issued date
2004
Volume
14
Number
21
Pages
1929-1934
Language
english
Abstract
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.
Keywords
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
Yes
Create date
24/01/2008 15:19
Last modification date
20/08/2019 16:18
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