Inflammasomes: current understanding and open questions

Cell Mol Life Sci. 2011 Mar;68(5):765-83. doi: 10.1007/s00018-010-0567-4. Epub 2010 Oct 31.

Abstract

The innate immune system relies on its capability to detect invading microbes, tissue damage, or stress via evolutionarily conserved receptors. The nucleotide-binding domain leucine-rich repeat (NLR)-containing family of pattern recognition receptors includes several proteins that drive inflammation in response to a wide variety of molecular patterns. In particular, the NLRs that participate in the formation of a molecular scaffold termed the "inflammasome" have been intensively studied in past years. Inflammasome activation by multiple types of tissue damage or by pathogen-associated signatures results in the autocatalytic cleavage of caspase-1 and ultimately leads to the processing and thus secretion of pro-inflammatory cytokines, most importantly interleukin (IL)-1β and IL-18. Here, we review the current knowledge of mechanisms leading to the activation of inflammasomes. In particular, we focus on the controversial molecular mechanisms that regulate NLRP3 signaling and highlight recent advancements in DNA sensing by the inflammasome receptor AIM2.

Publication types

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

MeSH terms

  • Adaptor Proteins, Signal Transducing / chemistry
  • Adaptor Proteins, Signal Transducing / physiology
  • Apoptosis Regulatory Proteins / chemistry
  • Apoptosis Regulatory Proteins / physiology
  • CARD Signaling Adaptor Proteins / chemistry
  • CARD Signaling Adaptor Proteins / physiology
  • Calcium-Binding Proteins / chemistry
  • Calcium-Binding Proteins / physiology
  • Carrier Proteins / chemistry
  • Carrier Proteins / physiology
  • Caspase 1 / metabolism
  • DNA-Binding Proteins
  • Humans
  • Immunity, Innate*
  • Inflammasomes / physiology*
  • Interleukin-1beta / metabolism
  • Interleukin-1beta / physiology
  • Models, Immunological*
  • NLR Family, Pyrin Domain-Containing 3 Protein
  • Nuclear Proteins / chemistry
  • Nuclear Proteins / physiology
  • Signal Transduction

Substances

  • AIM2 protein, human
  • Adaptor Proteins, Signal Transducing
  • Apoptosis Regulatory Proteins
  • CARD Signaling Adaptor Proteins
  • Calcium-Binding Proteins
  • Carrier Proteins
  • DNA-Binding Proteins
  • Inflammasomes
  • Interleukin-1beta
  • NLR Family, Pyrin Domain-Containing 3 Protein
  • NLRC4 protein, human
  • NLRP1 protein, human
  • NLRP3 protein, human
  • Nuclear Proteins
  • Caspase 1