Regulation of cGAS and STING signaling during inflammation and infection

Chauvin, Samuel D.; Stinson, William A.; Platt, Derek J.; Poddar, Subhajit; Miner, Jonathan J.

doi:10.1016/j.jbc.2023.104866

Cited by 12 publications

(1 citation statement)

References 192 publications

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“…Fishes 2023, 8, 597 2 of 14 result in the induction of downstream anti-microbial effector genes [1]. The stimulator of interferon genes (STING), also known as the mediator of IRF3 (IRF3) activation (MITA), endoplasmic reticulum interferon stimulator (ERIS), membrane tetraspanner (MPYS), and transmembrane protein 173 (TMEM173), has been identified as a central adaptor in the innate immune response to cytosolic DNA [2][3][4][5]. In mammals, STING functions downstream of the mitochondrial antiviral signaling protein (MAVS) and upstream of TANK-binding kinase 1 (TBK1) and interferon regulatory factors 3 in the retinoic acid inducible gene-I (RIG-I)-like receptors (RLRs)-mediated signaling pathway.…”

Section: Introductionmentioning

confidence: 99%

Identification and Characterization of the Stimulator of Interferon Genes (STING) in Chinese Giant Salamander Andrias davidianus

Chen,

Wang,

Wang

et al. 2023

Fishes

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The stimulator of interferon genes (STING) is a central and multifaceted mediator in innate immunity, and plays vital roles in defending against pathogen infection. In this study, we identified and functionally characterized the STING homolog from the Chinese giant salamander Andrias davidianus (AdSTING) for the first time. The open reading frame of AdSTING encodes a 362 amino acid protein with a predicted molecular mass of 41.6 kDa, which shares 31.1–46.7% of its sequence identity with STING homologs in other vertebrates. Structural analysis revealed that AdSTING possesses four predicted transmembrane domains (TMs) at the N-terminal, and a C-terminal domain (CTD) featuring a dimerization domain (DD), a c-di-GMP-binding domain (CBD), and a short C-terminal tail (CTT). Tissue distribution analysis showed that AdSTING mRNA was ubiquitously expressed in all examined tissues, with abundant expression in muscles, intestine, and thymus. During Andrias davidianus ranavirus (ADRV) infection, significant up-regulation of AdSTING expression was observed in the thymus, spleen, and kidney. Upon different stimuli in vitro, the expression of AdSTING was significantly induced by ADRV infection or polyinosin-polycytidylic acid (poly I:C) stimulation, but no obvious changes were observed during lipopolysaccharide (LPS) stimulation. Subcellular localization analysis revealed that AdSTING mainly localized in the cytoplasm in the Chinese giant salamander thymus cell line (GSTC) and co-localized with the endoplasmic reticulum (ER). Luciferase reporter assays confirmed the ability of AdSTING to activate the interferon-stimulated response element (ISRE) and interferon (IFN) promoter. Furthermore, overexpression of AdSTING effectively decreased ADRV infection, as evidenced by the reduction of virus titers and viral gene expression. Collectively, our findings underscore the pivotal role of AdSTING in the antiviral innate immunity of the Chinese giant salamander, offering insights into the functional evolution of STING in amphibians.

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Section: Introductionmentioning

confidence: 99%

Identification and Characterization of the Stimulator of Interferon Genes (STING) in Chinese Giant Salamander Andrias davidianus

Chen,

Wang,

Wang

et al. 2023

Fishes

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Regulation of Type I Interferon and Autophagy in Immunity against Mycobacterium Tuberculosis: Role of CGAS and STING1

Malik,

Shariq,

Sheikh

et al. 2024

Advanced Biology

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Mycobacterium tuberculosis (M. tb) is a significant intracellular pathogen responsible for numerous infectious disease‐related deaths worldwide. It uses ESX‐1 T7SS to damage phagosomes and to enter the cytosol of host cells after phagocytosis. During infection, M. tb and host mitochondria release dsDNA, which activates the CGAS‐STING1 pathway. This pathway leads to the production of type I interferons and proinflammatory cytokines and activates autophagy, which targets and degrades bacteria within autophagosomes. However, the role of type I IFNs in immunity against M. tb is controversial. While previous research has suggested a protective role, recent findings from cgas‐sting1 knockout mouse studies have contradicted this. Additionally, a study using knockout mice and non‐human primate models uncovered a new mechanism by which neutrophils recruited to lung infections form neutrophil extracellular traps. Activating plasmacytoid dendritic cells causes them to produce type I IFNs, which interfere with the function of interstitial macrophages and increase the likelihood of tuberculosis. Notably, M. tb uses its virulence proteins to disrupt the CGAS‐STING1 signaling pathway leading to enhanced pathogenesis. Investigating the CGAS‐STING1 pathway can help develop new ways to fight tuberculosis.

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The molecular mechanism of dsDNA sensing through the cGAS-STING pathway

Shinde,

2024

Advances in Immunology

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Regulation of cGAS and STING signaling during inflammation and infection

Cited by 12 publications

References 192 publications

Identification and Characterization of the Stimulator of Interferon Genes (STING) in Chinese Giant Salamander Andrias davidianus

Identification and Characterization of the Stimulator of Interferon Genes (STING) in Chinese Giant Salamander Andrias davidianus

Regulation of Type I Interferon and Autophagy in Immunity against Mycobacterium Tuberculosis: Role of CGAS and STING1

The molecular mechanism of dsDNA sensing through the cGAS-STING pathway

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