NLRC3, a member of the NLR family of proteins, is a negative regulator of innate immune signaling induced by the DNA sensor STING
Authors: Alex Petrucelli
Monika Schneider
Yan Jiang
Songying Ouyang
Joseph A Duncan
Zhi-Jie Liu
Hong-Bing Shu
Jinyao Mo
Blossom Damania
Jenny P-Y Ting
Zhigang Zhang
Lu Zhang
Haitao Wen
Sean M Gregory
Katherine A Fitzgerald
Karen V Swanson
Journal: Immunity (2014)
Discipline: IMMUNOLOGY
Keywords: STING; NLRC3; TBK1; innate immunity; type I interferon
Affiliations: Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; Department of Oral Biology, School of Dentistry, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA., Department of Medicine, Division of Infectious Diseases, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA., Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA., Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA., National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China., Division of Infectious Disease and Immunology, Department of Medicine, University of Massachusetts Medical School, Worcester, MA 01605, USA., iHuman Institute, ShanghaiTech University, Shanghai 201210, China., Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA., State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan 430072, China., Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; Institute of Inflammatory Diseases and Center for Translational Immunology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA. Electronic address: .

Abstract:  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. 

Retracted: No

PubPeer comments:
 Reverse primer for mIFNu03b2 simply repeated forward primer. , 
 Reverse primer for mIFNu03b2 simply repeated forward primer. This would be an honest mistake. ![file] ,