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. Author manuscript; available in PMC: 2020 Jun 23.
Published in final edited form as: Nat Rev Immunol. 2019 Mar 1;19(3):141–153. doi: 10.1038/s41577-018-0117-0

Figure 1. Hallmark cytokine responses induced by DNA-sensing PRRs.

Figure 1

(A) DNA originating from microbes, mitochondria, phagocytosed apoptotic cells, or leaked from the nucleus can accumulate in the cytoplasm where it is sensed by pattern recognition receptors. This initiates danger signaling. (B-D) Type I IFN and IL-1β production are the most studied immunological responses downstream of cytosolic DNA. (B) TLR9 senses CpG-rich DNA in endosomes and signals via MyD88 to activate IRF7, which is abundantly expressed in plasmacytoid dendritic cells. This leads to strong activation of genes encoding IFNα. (C) dsDNA in the cytoplasm is also sensed by AIM2, which promotes assembly of inflammasomes with caspase 1 activation, and downstream cleavage of pro-IL-1β to the bioactive cytokine. (D) dsDNA is sensed by cGAS, leading to enzymatic activation and synthesis of the STING agonist 2’3’cGAMP, thus leading to activation of the kinase TBK1, phosphorylation of the transcription factor IRF3, and transcriptional activation of the promotors for the type I (α/β) and type III (λ) IFN genes. Abbreviations not defined in the text: HTLV-I, Human T-lymphotropic virus I; IKK, IκB kinase; IRAK, Interleukin-1 receptor-associated kinase; Trex, Three prime repair exonuclease.