How the Innate Immune DNA Sensing cGAS-STING Pathway Is Involved in Autophagy

The cGAS-STING pathway is a key component of the innate immune system and exerts crucial roles in the detection of cytosolic DNA and invading pathogens. Accumulating evidence suggests that the intrinsic cGAS-STING pathway not only facilitates the production of type I interferons (IFN-I) and inflamma...

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Bibliographic Details
Published in:International journal of molecular sciences 2021-12, Vol.22 (24), p.13232
Main Authors: Zheng, Wanglong, Xia, Nengwen, Zhang, Jiajia, Chen, Nanhua, Meurens, François, Liu, Zongping, Zhu, Jianzhong
Format: Article
Language:English
Subjects:
Animals
Autophagy
Beclin-1 - metabolism
Binding sites
Biosynthesis
cGAS
Chromosomes
Cytokines
Deoxyribonucleic acid
DNA
DNA - immunology
DNA sensing
Endoplasmic reticulum
Herpes viruses
Homeostasis
Humans
IFN
Immune response
Immune system
Immunity, Innate
Inflammation
Injury prevention
Innate immunity
Insects
Interferon
Kinases
Life Sciences
Lipids
Liquid phases
Membrane Proteins - metabolism
Membranes
Microtubule-Associated Proteins - metabolism
Mitochondrial DNA
Nucleotidyltransferases - metabolism
Pathogens
Phagocytosis
Phase separation
Proteins
Review
Signal Transduction
STING
TOR protein
Tumors
Zika virus
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Summary:The cGAS-STING pathway is a key component of the innate immune system and exerts crucial roles in the detection of cytosolic DNA and invading pathogens. Accumulating evidence suggests that the intrinsic cGAS-STING pathway not only facilitates the production of type I interferons (IFN-I) and inflammatory responses but also triggers autophagy. Autophagy is a homeostatic process that exerts multiple effects on innate immunity. However, systematic evidence linking the cGAS-STING pathway and autophagy is still lacking. Therefore, one goal of this review is to summarize the known mechanisms of autophagy induced by the cGAS-STING pathway and their consequences. The cGAS-STING pathway can trigger canonical autophagy through liquid-phase separation of the cGAS-DNA complex, interaction of cGAS and Beclin-1, and STING-triggered ER stress-mTOR signaling. Furthermore, both cGAS and STING can induce non-canonical autophagy via LC3-interacting regions and binding with LC3. Subsequently, autophagy induced by the cGAS-STING pathway plays crucial roles in balancing innate immune responses, maintaining intracellular environmental homeostasis, alleviating liver injury, and limiting tumor growth and transformation.
ISSN:1422-0067
1661-6596
1422-0067
DOI:10.3390/ijms222413232