title: The PYRIN domain-only protein POP3 inhibits ALR inflammasomes and regulates responses to infection with DNA viruses.
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.
authors: Division of Rheumatology, Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA.
authors: Sonal
authors: S
authors: Khare
authors: Division of Rheumatology, Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA.
authors: Rojo A
authors: RA
authors: Ratsimandresy
authors: Division of Rheumatology, Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA.
authors: Lúcia
authors: L
authors: de Almeida
authors: Division of Rheumatology, Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA.
authors: Carla M
authors: CM
authors: Cuda
authors: 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.
authors: Stephanie L
authors: SL
authors: Rellick
authors: Division of Rheumatology, Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA.
authors: Alexander V
authors: AV
authors: Misharin
authors: Division of Rheumatology, Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA.
authors: Melissa C
authors: MC
authors: Wallin
authors: Division of Rheumatology, Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA.
authors: Anu
authors: A
authors: Gangopadhyay
authors: Department of Microbiology and Immunology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA.
authors: Eleonora
authors: E
authors: Forte
authors: Department of Microbiology and Immunology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA.
authors: Eva
authors: E
authors: Gottwein
authors: Division of Rheumatology, Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA.
authors: Harris
authors: H
authors: Perlman
authors: 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.
authors: John C
authors: JC
authors: Reed
authors: Sir William Dunn School of Pathology, University of Oxford, Oxford, UK.
authors: David R
authors: DR
authors: Greaves
authors: Division of Rheumatology, Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA.
authors: Andrea
authors: A
authors: Dorfleutner
authors: 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.
authors: Christian
authors: C
authors: Stehlik
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism*; D000595:Amino Acid Sequence; D000818:Animals; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D020170:Caspase 1 / Q000378:metabolism; D004266:DNA Virus Infections / Q000276:immunology*; D004267:DNA Viruses / Q000276:immunology*; D004268:DNA-Binding Proteins; D057809:HEK293 Cells; D006801:Humans; D007109:Immunity / Q000235:genetics; D058847:Inflammasomes / Q000378:metabolism*; D007370:Interferon Type I / Q000235:genetics / Q000276:immunology; D007371:Interferon-gamma / Q000235:genetics / Q000276:immunology; D008264:Macrophages / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D046912:Multiprotein Complexes / Q000235:genetics / Q000378:metabolism; D009687:Nuclear Proteins / Q000378:metabolism*; D011485:Protein Binding / Q000235:genetics; D017434:Protein Structure, Tertiary / Q000235:genetics; D016415:Sequence Alignment; D019076:Transgenes / Q000235:genetics; D014764:Viral Proteins / Q000235:genetics; D000076242:mTOR Associated Protein, LST8 Homolog
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C540422:Aim2 protein, mouse; D002352:Carrier Proteins; D004268:DNA-Binding Proteins; D058847:Inflammasomes; D007370:Interferon Type I; C555285:MLST8 protein, human; D046912:Multiprotein Complexes; D009687:Nuclear Proteins; D014764:Viral Proteins; D000076242:mTOR Associated Protein, LST8 Homolog; D007371:Interferon-gamma; D020170:Caspase 1