Emerging Activators and Regulators of Inflammasomes and Pyroptosis

Trends Immunol. 2019 Nov;40(11):1035-1052. doi: 10.1016/j.it.2019.09.005. Epub 2019 Oct 29.

Abstract

The inflammasome is a cytosolic immune signaling complex that induces inflammation and pyroptosis. Inflammasome complexes respond to a variety of pathogens, as well as danger or homeostasis-altering signals; they can play critical roles in the development of autoinflammatory conditions and cancer. Studies have now provided additional insights into the activation mechanisms and regulation of established inflammasome complexes, including NLRP1b, NLRP3, NOD-like receptor family apoptosis inhibitory protein (NAIP)-NLRC4, absent in melanoma (AIM)2, caspase-11, and pyrin. New activators and regulators of emerging NLRP6 and NLRP9b inflammasome complexes have also been described. We highlight the latest progress in our understanding of the molecular mechanisms governing inflammasome activation and pyroptosis, including the discovery of the pore-forming protein gasdermin D (GSDMD). We also discuss the importance of inflammasome activators and regulators in health and disease.

Keywords: AIM2; NLRC4; NLRP1; NLRP3; caspase; pyrin.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Humans
  • Inflammasomes / immunology*
  • Inflammation / immunology*
  • Intracellular Signaling Peptides and Proteins / metabolism
  • Mice
  • Pathogen-Associated Molecular Pattern Molecules / immunology*
  • Phosphate-Binding Proteins / metabolism
  • Pyroptosis
  • Receptors, G-Protein-Coupled / metabolism

Substances

  • CXCR5 protein, mouse
  • GSDMD protein, human
  • Inflammasomes
  • Intracellular Signaling Peptides and Proteins
  • NLRP6 protein, human
  • Pathogen-Associated Molecular Pattern Molecules
  • Phosphate-Binding Proteins
  • Receptors, G-Protein-Coupled