Science · 2013 · 1.1K citations · 19 references
Life SciencesImmunologyMolecular BiologyCell SignalingInnate ImmunitySignal TransductionAntiviral ImmunityDna VaccinesInnate Immune ActivationInnate Immune ResponseInnate Immune Signaling PathwaysInterferon ResponsesAntiviral Innate Immune SignalingAntiviral Innate SignalingAntiviral Interferon ResponsesCyclic Gmp-amp Synthase SignalingCytosolic Dna SensorsInterferon-mediated Antiviral DefenseType I Interferon PathwaysType I Interferon Responses
Cytosolic DNA signals danger by activating type I interferon responses, a key antiviral and DNA‑vaccine mechanism, and the enzyme cGAS has been identified as the primary sensor of this DNA. Knockout mouse studies show that cGAS is the essential DNA sensor for type I interferon responses across multiple cell types in vivo. Li et al.
Alarm Bells The presence of DNA in the cytosol of mammalian cells is a danger signal, indicating, for example, that a DNA-containing virus has infected the cell. This signal triggers an innate immune response, which involves the expression of type I interferons, and is critical for antiviral immunity and responses to DNA vaccines. Cyclic GMP-AMP synthase (cGAS) was recently identified as a sensor of cytosolic DNA. Li et al. (p. 1390 , published online 29 August) now use knockout mice to provide genetic evidence that, in multiple cell types, cGAS is the primary DNA sensor required for the type I interferon response in vivo.
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Cyclic GMP-AMP Synthase Is a Cytosolic DNA Sensor That Activates the Type I Interferon Pathway
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Cyclic GMP-AMP Is an Endogenous Second Messenger in Innate Immune Signaling by Cytosolic DNA
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