Immune sensing of DNA

By S. Paludan, A. Bowie. Immunity, 2013

749 citations recorded by the source corpus.

SUMMARY Although it has been appreciated for some years that cytosolic DNA is immune-stimulatory, it is only in the past five years that the molecular basis of DNA sensing by the innate immune system has begun to be revealed. In particular it has been described how DNA induces type I interferon, central in anti-viral responses and a mediator of autoimmunity. While to date more than 10 cytosolic receptors of DNA have been proposed, STING is a key adaptor protein for most DNA sensing pathways, and we are now beginning to understand the signaling mechanisms for STING. In this review we describe the recent progress in understanding signaling mechanisms activated by DNA and the relevance of DNA sensing to pathogen responses and autoimmunity. We highlight new insights gained into how and why the immune system responds to both pathogen and self DNA, and define important questions that now need to be addressed in the field of innate immune activation by DNA.

Subfields: Immunology, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/058e2a0fc1c312f3e321a8f10227acfc7814bf31

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Immunology

1. G. Barber
2. Zhijian J. Chen
3. T. Abe
4. Y. Chiu
5. Xin Cai
6. C. Reis e Sousa
7. D. Goubau
8. Safia Deddouche

In Molecular Biology

1. Zhijian J. Chen
2. G. Barber
3. T. Abe
4. M. Lamkanfi
5. T. Gajewski
6. V. Dixit
7. Douglas R. Green
8. Xin Cai

Citations in the corpus

• Cytosolic-DNA-Mediated, STING-Dependent Proinflammatory Gene Induction Necessitates Canonical NF-κB Activation through TBK1 (2014, background): “The repertoire of cytosolic dsDNA-dependent induced genes, including those for type I interferon (IFN) and proinflammatory genes such as those for interleukin-6 (IL-6), IL-1 , and tumor necrosis factor alpha (TNF- ), is known to require the IRF3 and NF- B pathways (12).”
• The cGAS-cGAMP-STING pathway of cytosolic DNA sensing and signaling. (2014, background): “Prior to the identification of cyclic-GMP-AMP (cGAMP) synthase (cGAS), a number of other putative DNA sensors had been reported (Paludan and Bowie, 2013), none of which has been met with universal acceptance as the major DNA sensor.”
• STING-dependent Cytosolic DNA Sensing Promotes Radiation-induced Type I interferon-dependent Antitumor Immunity in Immunogenic Tumors (2014, background): “…challenge (days) Tu m or 0 5 10 15 20 25 0 ns Time after tumor challenge (days) Tu m or V which in turn activate the transcription factors IFN regulatory factor 3 (IRF3), signal transducer and activator of transcription (STAT6), and nuclear factor-kB (NF-kB), respectively (Paludan and Bowie, 2013).”
• Cytosolic Sensing of Viruses (2013, background): “The lack of redundancy among these receptors, as well as their role in other cellular functions, has led to the hypothesis that they might function as cytosolic DNA sensors only in certain cell types and/or in response to certain pathogens (Paludan and Bowie, 2013, in this issue).”
• Mechanisms and functions of inflammasomes. (2014, background): “We would add to this second class of PRRs the proteins that sense cytosolic DNA and trigger the production of type I interferon (Paludan and Bowie, 2013).”
• Caspase-8; regulating life and death (2017, methodology): “92 Multiple cytosolic DNA sensors have been described, including DAI, cGAS, IFI16, and AIM2 [reviewed in (127)] and most cytosolic DNA sensors signal through the adapter protein STING, which is present on mitochondria.”