Cytosolic DNA sensors (CDS)

Cytosolic DNA sensors are a diverse group of pattern recognition receptors (PRRs) that detect double-stranded DNA (dsDNA) within the cytoplasm, a compartment where DNA is typically absent in healthy cells. This sensing mechanism is a vital component of the innate immune system, evolved to identify DNA from invading pathogens such as viruses and bacteria, as well as endogenous 'self-DNA' leaked from damaged nuclei or mitochondria (1.3.1, 1.3.3). The most prominent sensor, cyclic GMP-AMP synthase (cGAS), catalyzes the production of the second messenger cGAMP upon DNA binding, which subsequently activates the stimulator of interferon genes (STING) pathway to induce type I interferons and proinflammatory cytokines (1.3.1, 1.4.2). Other sensors, such as Absent in Melanoma 2 (AIM2), trigger the assembly of the inflammasome, leading to the maturation of interleukins and pyroptotic cell death (1.1.2, 1.3.2). While essential for host defense, the chronic or inappropriate activation of these sensors by self-DNA is linked to autoimmune disorders like systemic lupus erythematosus and Aicardi-Goutières syndrome (1.4.2, 1.4.4). Conversely, pharmacological activation of these pathways is being explored as a potent strategy in cancer immunotherapy to turn 'cold' tumors 'hot' by enhancing antitumor immunity (1.5.1, 1.5.3). Consequently, both agonists and inhibitors of cytosolic DNA sensing components are currently under intense investigation for their therapeutic potential across a wide range of inflammatory and oncological conditions (1.5.1, 1.5.2).

Other names

Cytoplasmic DNA sensorsIntracellular DNA sensorsDNA-sensing pattern recognition receptorsCytosolic DNA-sensing pathway componentsDNA-sensing receptors

Activation or inhibition of the cGAS-STING and AIM2 inflammasome pathways to modulate the production of Type I interferons and proinflammatory cytokines.