Stimulator of interferon genes (STING), also known as transmembrane protein encoded by the STING1 gene.
Chromosome 5.
STING plays an important role in innate immunity.
STING serves a vital function in the innate immune defense and for initiating anti-tumor immune responses.
Stimulator of interferon genes (STING) induces type I interferon production when cells are infected with intracellular pathogens, such as viruses, mycobacteria and intracellular parasites:serves a vital function in the innate immune defense and for initiating anti-tumor immune responses.
STING functions as a cytosolic sensor of DNA in cells, and triggers a cascade of events that ultimately leads the production of type I interferon alongside other cytokines that activate an immune response.
Type I interferon, that is mediated by STING, protects infected cells and nearby cells from local infection by binding to the same cell that secretes it by autocrine signaling and nearby cells by paracrine signaling.
STING (Stimulator of Interferon Genes) activation is a critical component of the innate immune response, particularly in the detection of cytosolic DNA from pathogens or cellular damage.
STING is a transmembrane protein located in the endoplasmic reticulum (ER) and is activated by cyclic dinucleotides such as cyclic GMP-AMP (cGAMP), which are synthesized by the DNA sensor cyclic GMP-AMP synthase (cGAS) upon detection of double-stranded DNA (dsDNA) in the cytosol.
Upon binding to cGAMP, STING undergoes a conformational change that promotes its oligomerization, for downstream signaling.
This oligomerization facilitates the recruitment and activation for phosphorylation of the transcription factor IRF3, which translocates to the nucleus, where it induces the expression of type I interferons and other inflammatory cytokines.
Small-molecule agonists that can activate STING through mechanisms distinct from cGAMP.
The precise mechanisms of STING activation is crucial for developing strategies targeting STING in cancer immunotherapy, antiviral treatments, and the management of autoimmune diseases.
STING works as both a direct cytosolic DNA sensor (CDS) and an adaptor protein in Type I interferon signaling through different molecular mechanisms, and activates downstream transcription factors responsible for antiviral response and innate immune response against intracellular pathogens.
STING is expressed in hematopoietic cells in peripheral lymphoid tissues, including T lymphocytes, NK cells, myeloid cells and monocytes, and is highly expressed in lung, ovary, heart, smooth muscle, retina, bone marrow and vagina.
The subcellular localization of STING is as an endoplasmic reticulum protein, and associates in close proximity with mitochondria associated ER membrane, and in the autophagosome.
STING mediates the type I interferon production in response to intracellular DNA and a variety of intracellular pathogens, including viruses, intracellular bacteria and intracellular parasites.
Upon infection, STING from infected cells can sense the presence of nucleic acids from intracellular pathogens, and then induce interferon β and more than 10 forms of interferon α production.
Type I interferon produced by infected cells can find and bind to Interferon-alpha/beta receptor of nearby cells to protect cells from local infection.
STING elicits powerful type I interferon immunity against viral infection.
After viral entry, viral nucleic acids are present in the cytosol of infected cells.
After recognizing viral DNA, DNA sensors initiate the downstream signaling pathways by activating STING-mediated interferon response.
Adenovirus, herpes simplex virus, HSV-1 and HSV-2, as well as the negative-stranded RNA virus, vesicular stomatitis virus (VSV), have been shown to be able to activate a STING-dependent innate immune response.
STING deficiency in mice led to lethal susceptibility to HSV-1 infection due to the lack of a successful type I interferon response.
Intracellular bacteria, Listeria monocytogenes, have been shown to stimulate host immune response through STING.
STING may play an important role in the production of chemokines.
STING deficient monocytes are intrinsically defective in migration to the liver during Listeria monocytogenes infection.
STING protects host from Listeria monocytogenes infection by regulating monocyte migration.
STING may be an important molecule for protective immunity against infectious organisms.
Although type I IFN is absolutely critical for resistance to viruses, there is growing literature about the negative role of type I interferon in host immunity mediated by STING.
Plasmodium berghei genome and extracellular DNA from Mycobacterium tuberculosis have been shown to activate type I interferon through STING.
Perforation of the phagosome membrane mediated by ESX1 secretion system allows extracellular mycobacterial DNA to access host cytosolic DNA sensors, thus inducing the production of type I interferon in macrophages.
STING mediates type I interferon immune response by functioning as both a direct DNA sensor and a signaling adaptor protein.
It is suggested that STING is associated with the activation of selective autophagy.
Mycobacterium tuberculosis has been shown to produce cytosolic DNA ligands which activate STING, resulting in ubiquitination of bacteria and the subsequent recruitment of autophagy related proteins, all of which are required for ‘selective’ autophagic targeting and innate defense against M. tuberculosis.
STING coordinates multiple immune responses to infection
STING induces of interferons and STAT6-dependent response and selective autophagy response.