Host innate immune DNA-sensing pathways (DNA-sensing pathways)

Host innate immune DNA-sensing pathways are critical defense mechanisms that detect the presence of foreign or misplaced self-DNA within the cell [8, 15]. The primary components include cyclic GMP-AMP synthase (cGAS), which detects cytosolic DNA and produces the second messenger cGAMP, and the stimulator of interferon genes (STING), which activates downstream signaling to induce type I interferons and pro-inflammatory cytokines [1, 3, 10]. Other sensors include Toll-like receptor 9 (TLR9) in endosomes and AIM2 in the cytosol, which triggers inflammasome activation and pyroptosis [4, 5, 12]. These pathways play a dual role in human health: they are essential for anti-viral and anti-tumor immunity, but their chronic or inappropriate activation is linked to autoimmune and inflammatory disorders like systemic lupus erythematosus and Aicardi-Goutières syndrome [7, 11, 20]. Pharmacological modulation of these pathways involves developing STING agonists to enhance cancer immunotherapy and STING or cGAS inhibitors to treat autoinflammatory conditions [1, 3, 9, 13].

Other names

Cytosolic DNA-sensing pathwaycGAS-STING pathwayTLR9 signaling pathwayAIM2 inflammasome pathwayNucleic acid-sensing pathways

STING agonism, STING inhibition, TLR9 agonism, cGAS inhibition, AIM2 inhibition