The Inflammasomes: Guardians of the Body

Annu Rev Immunol. 2009;27:229-65. doi: 10.1146/annurev.immunol.021908.132715.

Abstract

The innate immune system relies on its capacity to rapidly detect invading pathogenic microbes as foreign and to eliminate them. The discovery of Toll-like receptors (TLRs) provided a class of membrane receptors that sense extracellular microbes and trigger antipathogen signaling cascades. More recently, intracellular microbial sensors have been identified, including NOD-like receptors (NLRs). Some of the NLRs also sense nonmicrobial danger signals and form large cytoplasmic complexes called inflammasomes that link the sensing of microbial products and metabolic stress to the proteolytic activation of the proinflammatory cytokines IL-1beta and IL-18. The NALP3 inflammasome has been associated with several autoinflammatory conditions including gout. Likewise, the NALP3 inflammasome is a crucial element in the adjuvant effect of aluminum and can direct a humoral adaptive immune response. In this review, we discuss the role of NLRs, and in particular the inflammasomes, in the recognition of microbial and danger components and the role they play in health and disease.

Publication types

  • Review

MeSH terms

  • Animals
  • Autoimmune Diseases / immunology*
  • Autoimmune Diseases / metabolism
  • Carrier Proteins / immunology*
  • Carrier Proteins / metabolism
  • Humans
  • Immunity, Innate
  • Inflammation / immunology*
  • Inflammation / metabolism
  • Interleukin-18 / immunology
  • Interleukin-18 / metabolism
  • Interleukin-1beta / immunology
  • Interleukin-1beta / metabolism
  • Mice
  • Nod Signaling Adaptor Proteins / immunology*
  • Nod Signaling Adaptor Proteins / metabolism
  • RNA Helicases / immunology*
  • RNA Helicases / metabolism
  • Reactive Oxygen Species / immunology
  • Reactive Oxygen Species / metabolism
  • Toll-Like Receptors / immunology*
  • Toll-Like Receptors / metabolism
  • Uric Acid / immunology
  • Uric Acid / metabolism

Substances

  • Carrier Proteins
  • Interleukin-18
  • Interleukin-1beta
  • Nod Signaling Adaptor Proteins
  • Reactive Oxygen Species
  • Toll-Like Receptors
  • Uric Acid
  • RNA Helicases