A 360° view of the inflammasome: Mechanisms of activation, cell death, and diseases

Katherine C Barnett; Sirui Li; Kaixin Liang; Jenny P-Y Ting

doi:10.1016/j.cell.2023.04.025

A 360° view of the inflammasome: Mechanisms of activation, cell death, and diseases

Cell. 2023 May 25;186(11):2288-2312. doi: 10.1016/j.cell.2023.04.025.

Authors

Katherine C Barnett¹, Sirui Li², Kaixin Liang³, Jenny P-Y Ting⁴

Affiliations

¹ Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA. Electronic address: barnettk@med.unc.edu.
² Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
³ Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; Oral and Craniofacial Biomedicine Program, Adams School of Dentistry, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
⁴ Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; Oral and Craniofacial Biomedicine Program, Adams School of Dentistry, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA. Electronic address: jenny_ting@med.unc.edu.

PMID: 37236155
PMCID: PMC10228754 (available on 2024-05-25)
DOI: 10.1016/j.cell.2023.04.025

Abstract

Inflammasomes are critical sentinels of the innate immune system that respond to threats to the host through recognition of distinct molecules, known as pathogen- or damage-associated molecular patterns (PAMPs/DAMPs), or disruptions of cellular homeostasis, referred to as homeostasis-altering molecular processes (HAMPs) or effector-triggered immunity (ETI). Several distinct proteins nucleate inflammasomes, including NLRP1, CARD8, NLRP3, NLRP6, NLRC4/NAIP, AIM2, pyrin, and caspases-4/-5/-11. This diverse array of sensors strengthens the inflammasome response through redundancy and plasticity. Here, we present an overview of these pathways, outlining the mechanisms of inflammasome formation, subcellular regulation, and pyroptosis, and discuss the wide-reaching effects of inflammasomes in human disease.

Keywords: AIM2; CARD8; GSDMD; IL-18; IL-1β; NLRC4; NLRP1; NLRP3; NLRP6; caspase-1; caspase-11; caspase-4; caspase-5; inflammasome; pyrin; pyroptosis.

Publication types

Research Support, N.I.H., Extramural
Review

MeSH terms

Apoptosis Regulatory Proteins / metabolism
CARD Signaling Adaptor Proteins / metabolism
Caspases / metabolism
Cell Death
Humans
Inflammasomes* / metabolism
NLR Family, Pyrin Domain-Containing 3 Protein / metabolism
Neoplasm Proteins / metabolism
Pyroptosis

Substances

Apoptosis Regulatory Proteins
CARD Signaling Adaptor Proteins
CARD8 protein, human
Caspases
Inflammasomes
Neoplasm Proteins
NLR Family, Pyrin Domain-Containing 3 Protein

Abstract

Publication types

MeSH terms

Substances

Grants and funding