2. Academic Validation
  3. The PYRIN domain-only protein POP3 inhibits ALR inflammasomes and regulates responses to infection with DNA viruses

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.
Sonal Khare 1,  Rojo A Ratsimandresy 1,  Lúcia de Almeida 1,  Carla M Cuda 1,  Stephanie L Rellick 2,  Alexander V Misharin 1,  Melissa C Wallin 1,  Anu Gangopadhyay 1,  Eleonora Forte 3,  Eva Gottwein 3,  Harris Perlman 1,  John C Reed 4,  David R Greaves 5,  Andrea Dorfleutner 1,  Christian Stehlik 6
Affiliations

Affiliations

  • 1 Division of Rheumatology, Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA.
  • 2 1] Program in Cancer Cell Biology, Health Sciences Center, West Virginia University, Morgantown, West Virginia, USA. [2] Present address: Center for Neuroscience, Health Sciences Center, West Virginia University, Morgantown, West Virginia, USA.
  • 3 Department of Microbiology and Immunology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA.
  • 4 1] Apoptosis and Cell Death Research Program, Sanford-Burnham Medical Research Institute, La Jolla, California, USA. [2] Pharma Research and Early Development, F. Hoffmann-La Roche, Basel, Switzerland.
  • 5 Sir William Dunn School of Pathology, University of Oxford, Oxford, UK.
  • 6 1] Division of Rheumatology, Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA. [2] Robert H. Lurie Comprehensive Cancer Center, Interdepartmental Immunobiology Center and Skin Disease Research Center, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA.
PMID: 24531343 DOI: 10.1038/ni.2829
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.

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