Innate DNA-sensing receptor (IDSRs)

Innate DNA-sensing receptors (IDSRs) are a specialized class of pattern recognition receptors (PRRs) responsible for detecting double-stranded DNA (dsDNA) in cellular compartments where it is normally absent, such as the cytoplasm or endosomes, which typically signals viral or bacterial infection (Paludan & Bowie, 2013). Major members of this group include cyclic GMP-AMP synthase (cGAS), Toll-like receptor 9 (TLR9), and Absent in melanoma 2 (AIM2) (Hornung et al., 2009; Sun et al., 2013). Upon binding DNA, these sensors initiate signaling cascades—most notably the cGAS-STING axis—that result in the production of type I interferons and pro-inflammatory cytokines to orchestrate an immune response (Chen et al., 2016). While essential for host defense, dysregulation or chronic activation of these sensors by self-DNA is a primary driver of autoimmune disorders like systemic lupus erythematosus (SLE) and Aicardi-Goutières syndrome (Crow, 2014). Consequently, these receptors are major therapeutic targets; agonists are being investigated to stimulate anti-tumor immunity in oncology, while inhibitors are being developed to treat chronic inflammatory and autoimmune conditions (Corrales et al., 2015).

Other names

DNA sensorsCytosolic DNA sensorsDNA-sensing pattern recognition receptorsDNA-sensing PRRs

Modulation of the cGAS-STING pathway to induce or suppress Type I Interferons; Antagonism of endosomal TLR9 to reduce inflammatory signaling; Activation of the AIM2 inflammasome to induce IL-1 beta secretion.