NLRC3, a member of the NLR family of proteins, is a negative regulator of innate immune signaling induced by the DNA sensor STING
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Publisher version
UMass Chan Affiliations
Department of Medicine, Division of Infectious Diseases and ImmunologyDocument Type
Journal ArticlePublication Date
2014-03-20Keywords
AnimalsCell Line
Cyclic GMP
Cytokines
DNA
Herpes Simplex
Herpesvirus 1, Human
Humans
*Immunity, Innate
Intercellular Signaling Peptides and ProteinsInterferon Type IMembrane ProteinsMiceMice, KnockoutProtein BindingProtein TransportProtein-Serine-Threonine Kinases*Signal TransductionAmino Acids, Peptides, and ProteinsBacteriaImmunityImmunology and Infectious DiseaseImmunology of Infectious DiseaseInfectious DiseaseNucleic Acids, Nucleotides, and NucleosidesViruses
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Stimulator of interferon genes (STING, also named MITA, MYPS, or ERIS) is an intracellular DNA sensor that induces type I interferon through its interaction with TANK-binding kinase 1 (TBK1). Here we found that the nucleotide-binding, leucine-rich-repeat-containing protein, NLRC3, reduced STING-dependent innate immune activation in response to cytosolic DNA, cyclic di-GMP (c-di-GMP), and DNA viruses. NLRC3 associated with both STING and TBK1 and impeded STING-TBK1 interaction and downstream type I interferon production. By using purified recombinant proteins, we found NLRC3 to interact directly with STING. Furthermore, NLRC3 prevented proper trafficking of STING to perinuclear and punctated region, known to be important for its activation. In animals, herpes simplex virus 1 (HSV-1)-infected Nlrc3(-/-) mice exhibited enhanced innate immunity and reduced morbidity and viral load. This demonstrates the intersection of two key pathways of innate immune regulation, NLR and STING, to fine tune host response to intracellular DNA, DNA virus, and c-di-GMP.Source
Immunity. 2014 Mar 20;40(3):329-41. doi: 10.1016/j.immuni.2014.01.010. Epub 2014 Feb 20. Link to article on publisher's siteDOI
10.1016/j.immuni.2014.01.010Permanent Link to this Item
http://hdl.handle.net/20.500.14038/34956PubMed ID
24560620Related Resources
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