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CD36: linking lipids to the NLRP3 inflammasome, atherogenesis and atherothrombosis

Cellular & Molecular Immunology volume 11, pages 8–10 (2014)Cite this article

A recent study published in Nature Immunology by Sheedy et al.1 indicates that uptake of modified low-density lipoprotein (LDL) by the scavenger receptor CD36 primes and activates the NLRP3 inflammasome, providing an early pathogenic pathway that links cholesterol accumulation to the chronic inflammatory process of atherosclerosis.1 Atherosclerosis arises from chronic vascular inflammation elicited by lipids. During the past few years, several studies have sought to identify the mechanistic link between lipids and inflammation in atherogenesis. Foam cell formation involves the phagocytosis of matrix-retained lipoproteins and the fluid-phase pinocytosis of aggregated lipoproteins by macrophages; however, a substantial body of evidence also suggests that oxidative modification of subendothelially accumulated LDL triggers the inflammatory process underlying atherosclerosis.

The scavenger receptors CD36 and SR-A mediate the majority of modified LDL uptake by macrophages in vitro. In Apoe−/− mice, these receptors have been implicated in atheroprogression by inducing pro-inflammatory gene expression and macrophage apoptosis.2 The inflammatory response of macrophages to atherogenic lipids depends on the cooperation of Toll-like receptor 4 (TLR4) and TLR6 with CD36. Oxidized LDL (oxLDL) sequestered by CD36 induces intracellular CD36–TLR4–TLR6 heteromerization, actiating NF-κB.3 Atherogenic lipid mediators, such as oxLDL, oxidized phospholipids, lipoproteins and fatty acids, also trigger an oxidative burst through the CD36–TLR2–TLR6 pathway, leading to apoptosis of endoplasmic reticulum-stressed cholesterol-overloaded foam cells.4 Defective efferocytosis of apoptotic cells then causes secondary necrosis, contributing to necrotic core formation in advanced plaques.

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  1. GIGA-Research, Human Genetics Unit, Laboratory of Thrombosis and Hemostasis, University of Liège, Liège, Belgium

    Cécile Oury

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  1. Cécile Oury
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Correspondence to Cécile Oury.

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Oury, C. CD36: linking lipids to the NLRP3 inflammasome, atherogenesis and atherothrombosis. Cell Mol Immunol 11, 8–10 (2014). https://doi.org/10.1038/cmi.2013.48

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