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The inflammasome recognizes cytosolic microbial and host DNA and triggers an innate immune response
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The inflammasome recognizes cytosolic microbial and host DNA and triggers an innate immune response
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Journal Article
The inflammasome recognizes cytosolic microbial and host DNA and triggers an innate immune response
2008
Overview
Activation of inflammasomes leads to maturation of the pro-inflammatory cytokine IL-1β; this study adds DNA to the growing list of exogenous and endogenous inflammasome activators.
The innate immune system recognizes nucleic acids during infection and tissue damage. Whereas viral RNA is detected by endosomal toll-like receptors (TLR3, TLR7, TLR8) and cytoplasmic RIG-I and MDA5, endosomal TLR9 and cytoplasmic DAI bind DNA
1
, resulting in the activation of nuclear factor-κB and interferon regulatory factor transcription factors. However, viruses also trigger pro-inflammatory responses
2
, which remain poorly defined. Here we show that internalized adenoviral DNA induces maturation of pro-interleukin-1β in macrophages, which is dependent on NALP3 and ASC, components of the innate cytosolic molecular complex termed the inflammasome. Correspondingly, NALP3- and ASC-deficient mice display reduced innate inflammatory responses to adenovirus particles. Inflammasome activation also occurs as a result of transfected cytosolic bacterial, viral and mammalian (host) DNA, but in this case sensing is dependent on ASC but not NALP3. The DNA-sensing pro-inflammatory pathway functions independently of TLRs and interferon regulatory factors. Thus, in addition to viral and bacterial components or danger signals in general, inflammasomes sense potentially dangerous cytoplasmic DNA, strengthening their central role in innate immunity.
Publisher
Nature Publishing Group UK,Nature Publishing,Nature Publishing Group
Subject
/ Animals
/ Apoptosis Regulatory Proteins
/ Biological and medical sciences
/ CARD Signaling Adaptor Proteins
/ Carrier Proteins - immunology
/ Cytoskeletal Proteins - deficiency
/ Cytoskeletal Proteins - genetics
/ Cytoskeletal Proteins - immunology
/ DNA
/ Fundamental and applied biological sciences. Psychology
/ Humanities and Social Sciences
/ Humans
/ Immunity, Innate - immunology
/ Interleukin-1beta - immunology
/ Interleukin-1beta - metabolism
/ Interleukin-1beta - secretion
/ letter
/ Macrophages, Peritoneal - immunology
/ Macrophages, Peritoneal - metabolism
/ Mammals
/ Mice
/ Molecular and cellular biology
/ NLR Family, Pyrin Domain-Containing 3 Protein
/ Protein Processing, Post-Translational
/ RNA
/ Rodents
/ Science
/ Viruses
