CD36 coordinates NLRP3 inflammasome activation by facilitating the intracellular nucleation from soluble to particulate ligands in sterile inflammation

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Author
Sheedy, Frederick J.
Grebe, Alena
Rayner, Katey J.
Kalantari, Parisa
Ramkhelawon, Bhama
Carpenter, Susan B.
Ediriweera, Hasini N.
Mullick, Adam E.
Golenbock, Douglas T.
Latz, Eicke
Fitzgerald, Katherine A.
Moore, Kathryn J.
Note: Order does not necessarily reflect citation order of authors.
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https://doi.org/10.1038/ni.2639Metadata
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Sheedy, F. J., A. Grebe, K. J. Rayner, P. Kalantari, B. Ramkhelawon, S. B. Carpenter, C. E. Becker, et al. 2013. “CD36 coordinates NLRP3 inflammasome activation by facilitating the intracellular nucleation from soluble to particulate ligands in sterile inflammation.” Nature immunology 14 (8): 812-820. doi:10.1038/ni.2639. http://dx.doi.org/10.1038/ni.2639.Abstract
Particulate ligands including cholesterol crystals and amyloid fibrils induce NLRP3-dependent production of interleukin-1β (IL-1β) in atherosclerosis, Alzheimer's disease and diabetes. Soluble endogenous ligands including oxidized-LDL, amyloid-β and amylin peptides accumulate in these diseases. Here we identify a CD36-mediated endocytic pathway that coordinates the intracellular conversion of these soluble ligands to crystals or fibrils, resulting in lysosomal disruption and NLRP3-inflammasome activation. Consequently, macrophages lacking CD36 failed to elicit IL-1β production in response to these ligands and targeting CD36 in atherosclerotic mice reduced serum IL-1β and plaque cholesterol crystal accumulation. Collectively, these 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.Other Sources
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3720827/pdf/Terms of Use
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