Regulation of inflammasomes by autophagy

J Allergy Clin Immunol. 2016 Jul;138(1):28-36. doi: 10.1016/j.jaci.2016.05.009. Epub 2016 May 24.

Abstract

Inflammasomes detect pathogen-associated molecular patterns to induce inflammatory innate immune responses and play a key role in host defense against infectious agents. However, inflammasomes are often wrongly activated by metabolites, amyloids, and environmental irritants. This induces massive inflammation, causing severe tissue damage, and results in the development of inflammatory diseases. Hence cellular machineries regulating both "activation" and "inactivation" of inflammasomes are definitely important. Recent studies have shown that autophagy, an intracellular degradation system associated with maintenance of cellular homeostasis, plays a key role in inflammasome inactivation. Notably, autophagy deficiency caused by gene mutation disrupts organelle elimination and thus induces aberrant activation of inflammasomes, leading to severe tissue damage. Here we review recent findings regarding the involvement of autophagy in the regulation of inflammasome activation and development of inflammatory disorders.

Keywords: Autophagy; host defense; inflammasome; inflammatory disorders; innate immunity; macrophages; organelle; pattern recognition receptors; reactive oxygen species; signal transduction.

Publication types

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

MeSH terms

  • Animals
  • Autophagosomes / immunology
  • Autophagosomes / metabolism
  • Autophagy* / genetics
  • Autophagy* / immunology
  • Autophagy-Related Proteins / genetics
  • Autophagy-Related Proteins / metabolism
  • CARD Signaling Adaptor Proteins
  • Cytoskeletal Proteins / metabolism
  • Host-Pathogen Interactions / genetics
  • Host-Pathogen Interactions / immunology
  • Humans
  • Immunity, Innate
  • Inflammasomes / metabolism*
  • Inflammation / genetics
  • Inflammation / immunology
  • Inflammation / metabolism
  • Interleukin-1beta / metabolism
  • Lipopolysaccharides / immunology
  • Signal Transduction
  • Ubiquitination

Substances

  • Autophagy-Related Proteins
  • CARD Signaling Adaptor Proteins
  • Cytoskeletal Proteins
  • Inflammasomes
  • Interleukin-1beta
  • Lipopolysaccharides
  • PYCARD protein, human