Fig. 1.

Cytoplasmic nucleic acid recognition and type I IFN pathway activation. Scheme of cytoplasmic nucleotide sensing, type I IFN secretion and autocrine and paracrine IFNAR activation. Colored in blue are some of the proteins mutated in type I interferonopathies. Pathways currently not fully understood are identified with a question mark. cGAMP: cyclic di-GMP-AMP, cGAS: cyclic GMP-AMP synthase, ER: endothelial reticulum, ERGIC: endothelial reticulum-Golgi intermediate compartment, IFIH1: IFN-induced helicase C domain-containing protein 1 (also known as MDA5), IFNAR: interferon-α receptor, ISG15: interferon-stimulated gene 15, MAVS: mitochondrial antiviral-signaling protein, RIG-I: retinoic acid-inducible gene 1, SAMHD1: deoxynucleoside triphosphate triphosphohydrolase SAM domain and HD domain 1, STING: stimulator of interferon genes, TBK1: TANK-binding kinase 1, TREX1: DNA 3ʹ repair exonuclease 1, USP18: ubiquitin-specific protease 18