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CD36 ligands promote sterile inflammation through assembly of a Toll-like receptor 4 and 6 heterodimer.
- Source :
-
Nature immunology [Nat Immunol] 2010 Feb; Vol. 11 (2), pp. 155-61. Date of Electronic Publication: 2009 Dec 27. - Publication Year :
- 2010
-
Abstract
- In atherosclerosis and Alzheimer's disease, deposition of the altered self components oxidized low-density lipoprotein (LDL) and amyloid-beta triggers a protracted sterile inflammatory response. Although chronic stimulation of the innate immune system is believed to underlie the pathology of these diseases, the molecular mechanisms of activation remain unclear. Here we show that oxidized LDL and amyloid-beta trigger inflammatory signaling through a heterodimer of Toll-like receptors 4 and 6. Assembly of this newly identified heterodimer is regulated by signals from the scavenger receptor CD36, a common receptor for these disparate ligands. Our results identify CD36-TLR4-TLR6 activation as a common molecular mechanism by which atherogenic lipids and amyloid-beta stimulate sterile inflammation and suggest a new model of TLR heterodimerization triggered by coreceptor signaling events.
- Subjects :
- Amyloid beta-Peptides immunology
Animals
Atherosclerosis immunology
Atherosclerosis metabolism
Blotting, Western
CD36 Antigens metabolism
Cell Line
Chemokines biosynthesis
Chemokines immunology
Gene Expression
Humans
Immunoprecipitation
Inflammation metabolism
Lipoproteins, LDL immunology
Mice
Mice, Inbred C57BL
Mice, Knockout
Microglia immunology
Microglia metabolism
Reverse Transcriptase Polymerase Chain Reaction
Toll-Like Receptor 4 metabolism
Toll-Like Receptor 6 metabolism
CD36 Antigens immunology
Inflammation immunology
Signal Transduction immunology
Toll-Like Receptor 4 immunology
Toll-Like Receptor 6 immunology
Subjects
Details
- Language :
- English
- ISSN :
- 1529-2916
- Volume :
- 11
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Nature immunology
- Publication Type :
- Academic Journal
- Accession number :
- 20037584
- Full Text :
- https://doi.org/10.1038/ni.1836