Title

CD36 ligands promote sterile inflammation through assembly of a Toll-like receptor 4 and 6 heterodimer

UMMS Affiliation

Department of Medicine, Division of Infectious Diseases and Immunology

Publication Date

2010-02-01

Document Type

Article

Disciplines

Immunity | Immunology and Infectious Disease | Immunology of Infectious Disease | Infectious Disease | Virology

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.

DOI of Published Version

10.1038/ni.1836

Source

Nat Immunol. 2010 Feb;11(2):155-61. doi: 10.1038/ni.1836. Epub 2009 Dec 27. Link to article on publisher's site

Journal/Book/Conference Title

Nature immunology

Comments

Full list of authors omitted for brevity. For full list see article.

Related Resources

Link to Article in PubMed

PubMed ID

20037584

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