Sensing DNA viruses and bacteria by intracellular DNA sensors

The innate immune system confers first-line defense against various pathogens including bacteria and viruses. Early detection of invading pathogens by the host depends on a limited number of specific pattern recognition receptors (PRRs) that detect pathogen associated molecular patterns (PAMPs) and activate signal transduction cascades that lead to activation of defense mechanisms. Among those sensors, RIG-I-like receptors (RLRs) play crucial roles in the detection of viruses by recognizing intracellular viral patterns such as viral RNAs to induce type-I interferon production. The discovery of intracellular RNA sensing mechanism by RIG-I prompted the investigations to find out intracellular DNA sensors. Recently, several proteins including DAI, AIM2, IFI16, and cGAS have been suggested as DNA sensing molecules to detect DNA viruses and bacteria, suggesting there are multiple receptors for microbial DNA. In this review, we discuss the current our understanding of sensing microbial DNA and subsequent induction of immune responses.