Crosstalk between Cytoplasmic RIG-I and STING Sensing Pathways

Abstract

Detection of evolutionary conserved molecules on microbial pathogens by host immune sensors represents the initial trigger of the immune response against infection. Cytosolic receptors sense viral and intracellular bacterial genomes, as well as nucleic acids produced during replication. Once activated, these sensors trigger multiple signaling cascades, converging on the production of type I interferons and proinflammatory cytokines. Although distinct classes of receptors are responsible for the RNA and DNA sensing, the downstream signaling components are physically and functionally interconnected. This review will highlight the importance of the crosstalk between RIG-I-MAVS RNA sensing and the cGAS-STING DNA sensing pathways in potentiating efficient antiviral responses. The potential of cGAS-STING manipulation as a component of cancer immunotherapy will also be reviewed.

Synergistic activation of p53 by actinomycin D and nutlin-3a is associated with the upregulation of crucial regulators and effectors of innate immunity

“…originates from the detection of RNA viruses (by RIG-I receptors) and both converge on the activation of IRF3 transcription factor, which directly stimulates the transcription of genes for type I interferons [18]. We found that in spite of strong upregulation of STING, interferons are not produced in our model, which can be inferred from the lack of STAT1 phosphorylation in cells exposed to CPT or A + N. Probably, the cells are primed for interferon production but they lack a specific trigger (e.g.…”

“…IRF3 and IRF7 bind to the response elements of many antiviral genes and stimulate their transcription, e.g. genes coding for interferon-α1 and interferon-β1, IFNA1 and IFNB1, respectively [18]. Some genes coding for innate immunity proteins are regulated by p53.…”

Antiviral responses against chicken respiratory infections: Focus on avian influenza virus and infectious bronchitis virus

“…STING as an adaptor molecule STING interacts with MAVS to enhance antiviral responses. In fact, STING is the main player to coordinate cross-talks between RNA and DNA sensing pathways [87]. In the absent of RIG-I in chickens, STING plays a critical role in the induction of type I IFNS in chickens.…”

STING modulators: Predictive significance in drug discovery

“…DNA derived from dying tumor cells can enter the cytosol of dendritic cells as a consequence of TLR9 ligation, phagocytosis, or cellecell contact, leading to the induction of STING signaling [81]. Meanwhile, RIG-I stimulation coupled with potentiation of the response by STING could impact adaptive immune responses in cancer immunotherapy [82]. Therefore, further insight into the mechanisms of TLRs, RLRs and STING-mediated innate immune signaling in cancer immune evasion, tumorigenesis and cancer development may lead to discovery of novel therapeutic targets for cancer therapy [79,83,84].…”