CD36 coordinates NLRP3 inflammasome activation by facilitating intracellular nucleation of soluble ligands into particulate ligands in sterile inflammation
Authors
Sheedy, Frederick J.Grebe, Alena
Rayner, Katey J.
Kalantari, Parisa
Ramkhelawon, Bhama
Carpenter, Susan B.
Becker, Christine E.
Ediriweera, Hasini N.
Mullick, Adam E.
Golenbock, Douglas T.
Stuart, Lynda M.
Latz, Eicke
Fitzgerald, Katherine A.
Moore, Kathryn J.
UMass Chan Affiliations
Department of Medicine, Division of Infectious Diseases and ImmunologyDocument Type
Journal ArticlePublication Date
2013-08-01Keywords
ImmunityImmunology and Infectious Disease
Immunology of Infectious Disease
Infectious Disease
Metadata
Show full item recordAbstract
Particulate ligands, including cholesterol crystals and amyloid fibrils, induce production of interleukin 1beta (IL-1beta) dependent on the cytoplasmic sensor NLRP3 in atherosclerosis, Alzheimer's disease and diabetes. Soluble endogenous ligands, including oxidized low-density lipoprotein (LDL), amyloid-beta and amylin peptides, accumulate in such diseases. Here we identify an endocytic pathway mediated by the pattern-recognition receptor CD36 that coordinated the intracellular conversion of those soluble ligands into crystals or fibrils, which resulted in lysosomal disruption and activation of the NLRP3 inflammasome. Consequently, macrophages that lacked CD36 failed to elicit IL-1beta production in response to those ligands, and targeting CD36 in atherosclerotic mice resulted in lower serum concentrations of IL-1beta and accumulation of cholesterol crystals in plaques. Collectively, our findings highlight the importance of CD36 in the accrual and nucleation of NLRP3 ligands from within the macrophage and position CD36 as a central regulator of inflammasome activation in sterile inflammation.Source
Nat Immunol. 2013 Aug;14(8):812-20. doi: 10.1038/ni.2639. Epub 2013 Jun 30. Link to article on publisher's site
DOI
10.1038/ni.2639Permanent Link to this Item
http://hdl.handle.net/20.500.14038/35151PubMed ID
23812099Related Resources
ae974a485f413a2113503eed53cd6c53
10.1038/ni.2639