STING regulates intracellular DNA-mediated, type I interferon-dependent innate immunity
By Hiroki Ishikawa, Zhe Ma, G. Barber. Nature, 2009
2,640 citations recorded by the source corpus.
The innate immune system is critical for the early detection of invading pathogens and for initiating cellular host defence countermeasures, which include the production of type I interferon (IFN). However, little is known about how the innate immune system is galvanized to respond to DNA-based microbes. Here we show that STING (stimulator of interferon genes) is critical for the induction of IFN by non-CpG intracellular DNA species produced by various DNA pathogens after infection. Murine embryonic fibroblasts, as well as antigen presenting cells such as macrophages and dendritic cells (exposed to intracellular B-form DNA, the DNA virus herpes simplex virus 1 (HSV-1) or bacteria Listeria monocytogenes), were found to require STING to initiate effective IFN production. Accordingly, Sting-knockout mice were susceptible to lethal infection after exposure to HSV-1. The importance of STING in facilitating DNA-mediated innate immune responses was further evident because cytotoxic T-cell responses induced by plasmid DNA vaccination were reduced in Sting-deficient animals. In the presence of intracellular DNA, STING relocalized with TANK-binding kinase 1 (TBK1) from the endoplasmic reticulum to perinuclear vesicles containing the exocyst component Sec5 (also known as EXOC2). Collectively, our studies indicate that STING is essential for host defence against DNA pathogens such as HSV-1 and facilitates the adjuvant activity of DNA-based vaccines.
Subfields: Immunology, Molecular Biology
View Paper: https://www.semanticscholar.org/paper/1098beb4c76eacfcc093a88d02d02a681585e7c4
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In Immunology
- Shizuo Akira
- Zhijian J. Chen
- Taro Kawai
- G. Barber
- O. Takeuchi
- R. Medzhitov
- Katherine A. Fitzgerald
- Himanshu Kumar
In Molecular Biology
- Shizuo Akira
- Zhijian J. Chen
- Taro Kawai
- O. Takeuchi
- Tuo Li
- G. Barber
- Katherine A. Fitzgerald
- Himanshu Kumar
Citations in the corpus
- Cytosolic-DNA-Mediated, STING-Dependent Proinflammatory Gene Induction Necessitates Canonical NF-κB Activation through TBK1 (2014, background): “Previous reports have shown that the activation of NF- B is reduced in MEFs or macrophages in response to STING-dependent dsDNA signaling (3, 5, 23, 24).”
- STING-Dependent Cytosolic DNA Sensing Mediates Innate Immune Recognition of Immunogenic Tumors (2014, background): “It has been reported that activated STING accumulates as aggregates in a perinuclear region (Ishikawa et al., 2009).”
- The helicase DDX41 senses intracellular DNA mediated by the adaptor STING in dendritic cells (2011, background): “Although the adaptor STING (also called TMEM173, ERIS, MPYS or MITA) has an essential role in sensing cytosolic DN”
- Cyclic GMP-AMP Synthase is Activated by Double-stranded DNA-Induced Oligomerization (2013, background): “The endoplasmic reticulum (ER) membrane-localized adaptor protein STING is essential for the responses to cytosolic DNA (Barber, 2011b; Ishikawa and Barber, 2008; Ishikawa et al., 2009; Sun et al., 2009; Zhong et al., 2009).”