Viral evasion of DNA-stimulated innate immune responses

Christensen, Maria H; Paludan, Søren R

Toll-like receptor (TLR) 9 was the first DNA sensor to be described. It is expressed in the endosomal membrane and monitors the endosomal content for unmethylated, CpG-rich DNA. 4 As host DNA is mostly methylated, and hence has a low CpG content, as opposed to microbial DNA, TLR9 detects foreign DNA based both on location and chemical composition of the DNA. TLR9 signals through the adaptor protein MyD88, resulting in activation of signaling pathways eventually leading to activation of the transcription factors interferon (IFN) regulatory factor (IRF) 7-and nuclear factor-kappa B (NF-κB), which in turn drive transcription of type I IFN subtypes and proinflammatory cytokines 2 ( Figure 1 ).