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. 2020 Sep 20;1:7. doi: 10.1186/s43556-020-00006-z

Fig. 2.

Fig. 2

Source and function of cytosolic DNA. The cytosolic dsDNA pool is composed of DNA originating from retroviruses, DNA viruses, mitotic defects, mitochondria, intracellular prokaryotes and DNA rupture debris from the nuclei. In the cytosol, these DNA are either degraded by DNase III and TREX1 or sensed by DNA sensors. Once sensed by cytosolic sensors including AIM2, RNaseIII, cGAS and DAI, a cascade of reactions are triggered. Downstream signal molecules regulate the expression of immune-related genes, eventually leading to DNA clearance or cell death. In addition, DNA also comes from dead cells and bacteria. Membrane vesicles are formed by endocytosis and DNA is transported into the cell. DNase II is localized in lysosomes and digests DNA from pathogens and dead cells that end up in this cellular compartment. TLR9 directly binds with the remaining unmethylated CpG DNA and triggers downstream immune activation, inducing the expression of inflammation-related genes