Table 2.

Characterization of the DNA sensing pathways.

Proposed DNA sensor	Ligand	Cite of DNA sensing	Mechanism	Biological Response	References
Toll-like receptor
TLR9	CpG DNA	Endosomes	Recognizes unmethylated CpG DNA and recruits the adaptor protein MyD88 to induce activation of NF-κB and IRF7	Type I IFN	Kawai and Akira, 2011
PYHIN Family
AIM2	Cytosolic dsDNA	Cytoplasm	Binds to DNA via AIM2 HIN200 domain and recruits ASC via a pyrin:pyrin homotypic interaction followed by subsequent caspase activation	IL-1β and IL-18	Hornung et al., 2009
IFI16	Cytosolic dsDNA Nuclear dsDNA	Cytoplasm, nucleus	1. Interacts with STING, and subsequently induces IRF-3 phosphorylation. 2. Activates inflammasome responses through ASC and caspase-1	IFN-β, IL-6, IL-1β	Kerur et al., 2011; Ansari et al., 2013; Johnson et al., 2013 Ansari et al., 2015
Nucleotidyl Transferase Family
cGAS	Cytosolic dsDNA Y-form DNA DNA-RNA hybrid	Cytoplasm, nucleus	Binds to DNA and catalyzes the synthesis of cGAMP that activate STING followed by subsequent activation of IRF3	IFN-β	Ablasser et al., 2013; Gao et al., 2013; Sun et al., 2013
Protein Kinase (PK) Family
DNA-PK	Cytosolic dsDNA	Cytoplasm	1. Senses DNA and activates the STING-TBK1-IRF3 axis 2. Induces STING independent DNA sensing pathway by triggering HSPA8 and IRF3 phosphorylation	IFN-λl, IFN-β, IL-6	Burleigh et al., 2020
Ku70	Cytosolic dsDNA	Cytoplasm	Senses DNA and induces the production of type III IFN	Type III IFN	Zhang et al., 2011
DExD/H-Box Helicase Family
DHX9 and DHX36	CpG DNA	Cytoplasm	Detect CpG DNA and activate an MyD88-dependent pathway	TNF-α, IFN-α	Kim et al., 2010
Other DNA sensors
DAI	Cytosolic dsDNA	Cytoplasm	Senses DNA and activates the STING-TBK1-IRF3 axis	IFN-β	Takaoka et al., 2007
Mre11	Cytosolic dsDNA	Cytoplasm	Senses DNA and activates the STING-TBK1-IRF3 axis	IFN-β	Kondo et al., 2013