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The PYRIN domain–only protein POP3 inhibits ALR inflammasomes and regulates responses to infection with DNA viruses
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The PYRIN domain–only protein POP3 inhibits ALR inflammasomes and regulates responses to infection with DNA viruses
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Journal Article
The PYRIN domain–only protein POP3 inhibits ALR inflammasomes and regulates responses to infection with DNA viruses
2014
Overview
Much is known about the activation of inflammasomes, but less is known about their negative regulation. Stehlik and colleagues demonstrate that the pyrin domain–only protein POP3 negatively regulates inflammasomes involved in sensing DNA.
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.
Publisher
Nature Publishing Group US,Nature Publishing Group
Subject
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/ Adaptor Proteins, Signal Transducing - genetics
/ Adaptor Proteins, Signal Transducing - metabolism
/ Animals
/ Carrier Proteins - metabolism
/ DNA
/ DNA Virus Infections - immunology
/ Humans
/ Interferon Type I - genetics
/ Interferon Type I - immunology
/ Interferon-gamma - immunology
/ Mice
/ mTOR Associated Protein, LST8 Homolog
/ Multiprotein Complexes - genetics
/ Multiprotein Complexes - metabolism
/ Nuclear Proteins - metabolism
/ Protein Structure, Tertiary - genetics
/ Proteins
