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