The helicase DDX41 senses intracellular DNA mediated by the adaptor STING in dendritic cells

By Zhiqiang Zhang, Bin Yuan, Musheng Bao, Ning Lu, Taeil Kim, Yong‐jun Liu. Nature Immunology, 2011

897 citations recorded by the source corpus.

The recognition of pathogenic DNA is important to the initiation of antiviral responses. Here we report the identification of DDX41, a member of the DEXDc family of helicases, as an intracellular DNA sensor in myeloid dendritic cells (mDCs). Knockdown of DDX41 expression by short hairpin RNA blocked the ability of mDCs to mount type I interferon and cytokine responses to DNA and DNA viruses. Overexpression of both DDX41 and the membrane-associated adaptor STING together had a synergistic effect in promoting Ifnb promoter activity. DDX41 bound both DNA and STING and localized together with STING in the cytosol. Knockdown of DDX41 expression blocked activation of the mitogen-activated protein kinase TBK1 and the transcription factors NF-κB and IRF3 by B-form DNA. Our results suggest that DDX41 is an additional DNA sensor that depends on STING to sense pathogenic DNA.

Subfields: Immunology, Infectious Diseases, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/c53673f10c14ca7640441d1bee04a45080c9e6ec

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In Immunology

In Infectious Diseases

Zhijian J. Chen

In Molecular Biology

Citations in the corpus

Cyclic [G(2′,5′)pA(3′,5′)p] Is the Metazoan Second Messenger Produced by DNA-Activated Cyclic GMP-AMP Synthase (2013, neutral): “, 2010), DDX41 (DEAD box polypeptide 41) (Zhang et al., 2011), and members of the HIN-200 (hematopoietic interferon-inducible nuclear proteins) family such as AIM2 (absent in melanoma 2) (Hornung et al.”
STING Specifies IRF3 phosphorylation by TBK1 in the Cytosolic DNA Signaling Pathway (2012, methodology): “Indeed, DDX41 interacts with STING in the region spanning the second to fourth transmembrane domains of STING (16).”
DEAD-Box Helicases: Sensors, Regulators, and Effectors for Antiviral Defense (2020, background): “Activation of the EGF growth factor receptor attenuates DDX60 activity, so viruses known to activate EGF including influenza A virus, RIG-I PPP Interferon (IFN) induction MAVS IFN MDA5 DDX60 TRAF3 TBK1 IKKε IRF3 IRF7 DDX3XP DAMP signaling DDX60 VSV RNA Interferon-stimulated gene (ISG) induction TRIF”
Dendritic-cell-based therapeutic cancer vaccines. (2013, background): “Nucleic acid detection can lead to the production of protective type I IFN via endosomal or cytoplasmic sensors (Barber, 2011; Desmet and Ishii, 2012; Zhang et al., 2011a; Zhang et al., 2011b).”
Cytosolic Sensing of Viruses (2013, background): “IFNs signal via the interferon receptor (IFNAR) and upregulate the expression of hundreds of ISGs, including the antiviral factors and PRRs themselves, as well as proteins important in regulating immune responses.”
Immune sensing of DNA (2013, neutral): “This raises important questions about the emerging roles of the DDX superfamily in intracellular sensing of nucleic acids (Zhang et al., 2011b, 2011c; Kim et al., 2010).”
Innate Immune Pattern Recognition: A Cell Biological Perspective (2015, neutral): “The helicase DDX41 senses intracellular DNA mediated by the adaptor STING in dendritic cells.”