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

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Abstract
The cGAS–STING signaling axis can be activated by cytosolic DNA, including both non-self DNA and self DNA. This axis is used by the innate immune system to monitor invading pathogens and/or damage. Increasing evidence has suggested that the cGAS-STING pathway not only facilitates inflammatory responses and the production of type I interferons (IFN), but also activates other cellular processes, such as apoptosis. Recently, many studies have focused on analyzing the mechanisms of apoptosis induced by the cGAS-STING pathway and their consequences. This review gives a detailed account of the interplay between the cGAS-STING pathway and apoptosis. The cGAS-STING pathway can induce apoptosis through ER stress, NLRP3, NF-κB, IRF3, and IFN signals. Conversely, apoptosis can feed back to regulate the cGAS-STING pathway, suppressing it via the activation of caspases or promoting it via mitochondrial DNA (mtDNA) release. Apoptosis mediated by the cGAS-STING pathway plays crucial roles in balancing innate immune responses, resisting infections, and limiting tumor growth.
Funding Information
  • National Natural Science Foundation of China (32202818, 32172867, 31872450, D18007)
  • 111 Project (32202818, 32172867, 31872450, D18007)
  • Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD) (32202818, 32172867, 31872450, D18007)

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