Lipid-protein interactions regulating the canonical and the non-canonical NLRP3 inflammasome

Abstract

The inflammatory response is a complex regulated effector mechanism of the innate immune system that is initiated after tissue injury or infection. The NLRP3 inflammasome is an important initiator of inflammation by regulating the activation of caspase-1, the maturation of pro-inflammatory cytokines and the induction of pyroptotic cell death. Numerous studies demonstrate that the NLRP3 inflammasome could be modulated by lipids, existing a relation between lipids and the activation of different inflammatory processes. In this review we will summarize how the mechanism of NLRP3 inflammasome activation is regulated by different lipids and how these lipids control specific cellular localization of NLRP3 during activation. Although being a cytosolic protein, NLRP3 interacts with lipids accessible in neighbor membranes. Also, the modulation of NLRP3 by endogenous lipids has been found causative of different metabolic diseases and bacterial-pathogenic lipids lead to NLRP3 activation during infection. The understanding of the modulation of the NLRP3 inflammasome by lipids has resulted not only in a better knowledge about the mechanism of NLRP3 activation and its implication in disease, but also opens a new avenue for the development of novel therapeutics and vaccines, as NLRP3 could be modulated by synthetic lipids used as adjuvants.

Keywords: 25-hydroxycholesterol; Cardiolipin; Caspase; Ceramide; Cholesterol; Inflammasome; Inflammation; Interleukin-1; Linoleic acid; Lipophosphoglycan; Lipopolysaccharide; Non-canonical inflammasome; Oleic acid; Ornithine lipid; Phosphatidylcholine; Phosphatidylinositol-4-phosphate; Polyunsaturated fatty acid; Pyroptosis; Saturated fatty acid; Sphingosine.