Trafficking of cholesterol to the ER is required for NLRP3 inflammasome activation.

ABSTRACT: Cellular lipids determine membrane integrity and fluidity and are being increasingly recognized to influence immune responses. Cellular cholesterol requirements are fulfilled through biosynthesis and uptake programs. In an intricate pathway involving the lysosomal cholesterol transporter NPC1, the sterol gets unequally distributed across intracellular compartments. By using pharmacological and genetic approaches targeting NPC1, we reveal that blockade of cholesterol trafficking through the late endosome-lysosome pathway blunts NLRP3 inflammasome activation. Altered cholesterol localization at the plasma membrane (PM) in Npc1^-/- cells abrogated AKT-mTOR signaling by TLR4. However, the inability to activate the NLRP3 inflammasome was traced to perturbed cholesterol traffick

SUBMITTER: de la Roche M 

PROVIDER: S-EPMC6168277 | biostudies-literature | 2018 Oct

REPOSITORIES: biostudies-literature