DNA recognition in immunity and disease

Great progress has been made in understanding how immune cells detect microbial pathogens. An area that has received particular attention is nucleic acid sensing where RNA and DNA sensing machineries have been uncovered. For DNA, TLR9 in endosomes and numerous cytoplasmic DNA binding proteins have been identified. Several of these have been proposed to couple DNA recognition to induction of type I IFNs, pro-inflammatory cytokines and/or caspase-1 activation. Given the ubiquitous expression of many of these DNA binding proteins and the significant potential for endogenous DNA to engage these molecules, it is important that DNA recognition is tightly regulated. A better understanding of DNA recognition pathways can provide new insights into infectious, inflammatory and autoimmune diseases.

► DNA sensing is a major means of pathogen detection.
► TLR9 and multiple cytoplasmic proteins detect DNA.
► DNA activates caspase-1 activating inflammasome.
► STING signaling is a major hub of DNA sensing.
► DNase limit activation of DNA sensors by endogenous ligands.