Innate immune DNA sensor (DNA sensor)

Innate immune DNA sensors are a diverse group of pattern recognition receptors (PRRs) that detect the presence of double-stranded DNA (dsDNA) in inappropriate cellular compartments, such as the cytoplasm or endosomes, which typically signals infection or cellular damage (PMID: 30635666). Key members include cyclic GMP-AMP synthase (cGAS), which produces the second messenger cGAMP to activate the Stimulator of Interferon Genes (STING) pathway, and Toll-like receptor 9 (TLR9), which recognizes unmethylated CpG motifs in endosomes (PMID: 28410988). Other sensors like Absent in melanoma 2 (AIM2) trigger the formation of the inflammasome, leading to IL-1β release and pyroptosis (PMID: 21327021). These sensors play a critical role in defending against viral and bacterial pathogens but can also be triggered by self-DNA in autoimmune conditions like systemic lupus erythematosus (SLE) (PMID: 31043709). In oncology, activating these pathways (particularly cGAS-STING) is a major strategy to turn cold tumors hot by promoting dendritic cell maturation and T-cell infiltration (PMID: 31439479). Conversely, inhibitors are being developed to treat autoinflammatory diseases driven by chronic DNA sensing (PMID: 30510223).

Other names

Cytosolic DNA sensorDNA-sensing pattern recognition receptorNucleic acid sensorIntracellular DNA sensor

Agonists bind to and activate sensors (e.g., STING, TLR9) to induce Type I interferons and pro-inflammatory cytokines for cancer immunotherapy; antagonists or inhibitors block DNA sensing or downstream signaling to treat autoimmune and autoinflammatory diseases (PMID: 30635666, 30510223).