The PYRIN domain-only protein POP3 inhibits ALR inflammasomes and regulates responses to infection with DNA viruses

Nat Immunol. 2014 Apr;15(4):343-53. doi: 10.1038/ni.2829. Epub 2014 Feb 16.

Abstract

The innate immune system responds to infection and tissue damage by activating cytosolic sensory complexes called 'inflammasomes'. Cytosolic DNA is sensed by AIM2-like receptors (ALRs) during bacterial and viral infections and in autoimmune diseases. Subsequently, recruitment of the inflammasome adaptor ASC links ALRs to the activation of caspase-1. A controlled immune response is crucial for maintaining homeostasis, but the regulation of ALR inflammasomes is poorly understood. Here we identified the PYRIN domain (PYD)-only protein POP3, which competes with ASC for recruitment to ALRs, as an inhibitor of DNA virus-induced activation of ALR inflammasomes in vivo. Data obtained with a mouse model with macrophage-specific POP3 expression emphasize the importance of the regulation of ALR inflammasomes in monocytes and macrophages.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics
  • Adaptor Proteins, Signal Transducing / metabolism*
  • Amino Acid Sequence
  • Animals
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism*
  • Caspase 1 / metabolism
  • DNA Virus Infections / immunology*
  • DNA Viruses / immunology*
  • DNA-Binding Proteins
  • HEK293 Cells
  • Humans
  • Immunity / genetics
  • Inflammasomes / metabolism*
  • Interferon Type I / genetics
  • Interferon Type I / immunology
  • Interferon-gamma / genetics
  • Interferon-gamma / immunology
  • Macrophages / immunology*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Molecular Sequence Data
  • Multiprotein Complexes / genetics
  • Multiprotein Complexes / metabolism
  • Nuclear Proteins / metabolism*
  • Protein Binding / genetics
  • Protein Structure, Tertiary / genetics
  • Sequence Alignment
  • Transgenes / genetics
  • Viral Proteins / genetics
  • mTOR Associated Protein, LST8 Homolog

Substances

  • Adaptor Proteins, Signal Transducing
  • Aim2 protein, mouse
  • Carrier Proteins
  • DNA-Binding Proteins
  • Inflammasomes
  • Interferon Type I
  • MLST8 protein, human
  • Multiprotein Complexes
  • Nuclear Proteins
  • Viral Proteins
  • mTOR Associated Protein, LST8 Homolog
  • Interferon-gamma
  • Caspase 1

Associated data

  • GENBANK/KF562078