Table 1 Classification of the cytosolic dsDNA that activates the cGAS-STING signaling axis

Self-DNA

Micronuclei

Rupture of the micronuclei membrane leads to exposure of chromatin DNA that is recognized by cGAS, which activates the cGAS-STING pathway.

[12]

Mitochondrion

Mitochondrial stress induces mtDNA leakage into the cytosol, thus activating the STING pathway and inducing production of cytokines.

[13]

Nuclear RNA

Facilitated by endogenous retroelements, nuclear RNA can be reversely transcribed into DNA that activates cGAS-STING signaling.

[10]

Pathogen-derived DNA

DNA virus

HSV1, HSV2, KSHV, adenovirus, vaccinia virus, cytomegalovirus, papillomavirus, murine gamma-herpesvirus 68

DNA viruses invade host cells and release pathogen-derived DNA to induce STING activation.

[14,15,16,17,18,19,20]

Retrovirus

HIV, SIV, murine leukemia virus

DNA intermediates generated from reverse transcription may be recognized by cGAS to stimulate downstream STING signaling.

[11]

RNA virus

West Nile virus, dengue virus, VSV, SARS-COV-2

Infection with RNA viruses might cause cellular damage and cell death, which results in the release of cellular DNA and further activation of the cGAS-STING axis; SARS-CoV-2 binding to ACE2 can lead to excessive angiotensin II signaling that activates the STING pathway in mice.

[21,22,23]

Bacteria

Listeria monocytogenes, Mycobacterium tuberculosis, Listeria, Shigella, Francisella, Chlamydia and Neisseria

Bacteria produce CDNs, such as cyclic di-GMP and cyclic di-AMP, which can directly bind to and activate STING.

[10, 24,25,26,27,28,29,30,31]