Activation of the STING-Dependent Type I Interferon Response Reduces Microglial Reactivity and Neuroinflammation

Mathur, Vidhu; Burai, Ritwik; Vest, Ryan; Bonanno, Liana; Lehallier, Benoit; Zardeneta, Macy E.; Mistry, Karishma N.; Do, Danny; Marsh, Samuel E.; Abud, Edsel M.; Blurton‐Jones, Mathew; Li, Lingyin; Lashuel, Hilal A.; Wyss‐Coray, Tony

doi:10.1016/j.neuron.2017.11.032

Cited by 129 publications

(121 citation statements)

References 52 publications

Supporting

Mentioning

113

Contrasting

Order By: Relevance

“…This implies a protective role for type-I IFN in CNS, which is considered to counteract the pro-inflammatory IFNγ (206). Using experimental autoimmune encephalitis (EAE) as a MS model, STING was found to be indispensable for amelioration of type-I IFNmediated neuroinflammation, and it could be induced by a conventional anti-viral drug ganciclovir (207). Ultraviolet (UV) radiation is a factor inversely related to the morbidity of MS (208).…”

Section: Cgas-sting Pathway In Autoimmune or Inflammatory Diseasesmentioning

confidence: 99%

Research Advances in How the cGAS-STING Pathway Controls the Cellular Inflammatory Response

2020

View full text Add to dashboard Cite

Double-stranded DNA (dsDNA) sensor cyclic-GMP-AMP synthase (cGAS) along with the downstream stimulator of interferon genes (STING) acting as essential immunesurveillance mediators have become hot topics of research. The intrinsic function of the cGAS-STING pathway facilitates type-I interferon (IFN) inflammatory signaling responses and other cellular processes such as autophagy, cell survival, senescence. cGAS-STING pathway interplays with other innate immune pathways, by which it participates in regulating infection, inflammatory disease, and cancer. The therapeutic approaches targeting this pathway show promise for future translation into clinical applications. Here, we present a review of the important previous works and recent advances regarding the cGAS-STING pathway, and provide a comprehensive understanding of the modulatory pattern of the cGAS-STING pathway under multifarious pathologic states.

show abstract

Section: Cgas-sting Pathway In Autoimmune or Inflammatory Diseasesmentioning

confidence: 99%

Research Advances in How the cGAS-STING Pathway Controls the Cellular Inflammatory Response

2020

View full text Add to dashboard Cite

show abstract

“…It will be interesting to observe the impact of Mϕ pyroptosis on the cGAS‐STING signaling pathway in above mentioned autoimmune diseases where NETosis plays a significant role in the immunopathogenesis. It is noteworthy that STING activation in microglia by an antiviral drug called ganciclovir decreases the microglial function and neuroinflammation in experimental autoimmune encephalomyelitis (EAE) …”

Section: Cgas‐sting Signaling In Autoinflammation and Autoimmunitymentioning

confidence: 99%

A STING to inflammation and autoimmunity

Kumar

2019

Journal of Leukocyte Biology

View full text Add to dashboard Cite

Various intracellular pattern recognition receptors (PRRs) recognize cytosolic pathogenassociated molecular patterns (PAMPs) and damage-associated molecular patterns (DAMPs). Cyclic GMP-AMP synthase (cGAS), a cytosolic PRR, recognizes cytosolic nucleic acids including dsDNAs. The recognition of dsDNA by cGAS generates cyclic GMP-AMP (GAMP). The cGAMP is then recognized by STING generating type 1 IFNs and NF-B-mediated generation of proinflammatory cytokines and molecules. Thus, cGAS-STING signaling mediated recognition of cytosolic dsDNA causing the induction of type 1 IFNs plays a crucial role in innate immunity against cytosolic pathogens, PAMPs, and DAMPs. The overactivation of this system may lead to the development of autoinflammation and autoimmune diseases. The article opens with the introduction of different PRRs involved in the intracellular recognition of dsDNA and gives a brief introduction of cGAS-STING signaling. The second section briefly describes cGAS as intracellular PRR required to recognize intracellular nucleic acids (dsDNA and CDNs) and the formation of cGAMP. The cGAMP acts as a second messenger to activate STING-and TANK-binding kinase 1-mediated generation of type 1 IFNs and the activation of NF-B. The third section of the article describes the role of cGAS-STING signaling in the induction of autoinflammation and various autoimmune diseases. The subsequent fourth section describes both chemical compounds developed and the endogenous negative regulators of cGAS-STING signaling required for its regulation. Therapeutic targeting of cGAS-STING signaling could offer new ways to treat inflammatory and autoimmune diseases. K E Y W O R D S

show abstract

“…STING protein is activated by direct interaction with cytosolic DNA, which is usually derived from intracellular viruses or bacteria or cyclic GMP-AMP synthetase and so on. Following activation, it induces interferon regulatory factor 3 that translocates to the cell nucleus and stimulates the transcription of type I interferons genes and also activates the NFκB signaling pathway [51,52].…”

Section: Mitochondrial Dna As a Stimulator Of Interferon Signalingmentioning

confidence: 99%

Mitochondrial DNA: A Key Regulator of Anti-Microbial Innate Immunity

Kausar

Yang

Abbas

et al. 2020

Genes

View full text Add to dashboard Cite

During the last few years, mitochondrial DNA has attained much attention as a modulator of immune responses. Due to common evolutionary origin, mitochondrial DNA shares various characteristic features with DNA of bacteria, as it consists of a remarkable number of unmethylated DNA as 2′-deoxyribose cytidine-phosphate-guanosine (CpG) islands. Due to this particular feature, mitochondrial DNA seems to be recognized as a pathogen-associated molecular pattern by the innate immune system. Under the normal physiological situation, mitochondrial DNA is enclosed in the double membrane structure of mitochondria. However, upon pathological conditions, it is usually released into the cytoplasm. Growing evidence suggests that this cytosolic mitochondrial DNA induces various innate immune signaling pathways involving NLRP3, toll-like receptor 9, and stimulator of interferon genes (STING) signaling, which participate in triggering downstream cascade and stimulating to produce effector molecules. Mitochondrial DNA is responsible for inflammatory diseases after stress and cellular damage. In addition, it is also involved in the anti-viral and anti-bacterial innate immunity. Thus, instead of entire mitochondrial importance in cellular metabolism and energy production, mitochondrial DNA seems to be essential in triggering innate anti-microbial immunity. Here, we describe existing knowledge on the involvement of mitochondrial DNA in the anti-microbial immunity by modulating the various immune signaling pathways.

show abstract

Activation of the STING-Dependent Type I Interferon Response Reduces Microglial Reactivity and Neuroinflammation

Cited by 129 publications

References 52 publications

Research Advances in How the cGAS-STING Pathway Controls the Cellular Inflammatory Response

Research Advances in How the cGAS-STING Pathway Controls the Cellular Inflammatory Response

A STING to inflammation and autoimmunity

Mitochondrial DNA: A Key Regulator of Anti-Microbial Innate Immunity

Contact Info

Product

Resources

About