Structural insights into ligand recognition and regulation of nucleic acid-sensing Toll-like receptors

Toll-like receptors (TLRs) activate the innate immune system in response to invading pathogens. Although nucleic acids are one of the principal TLR ligands, they are not inherently pathogen-specific and, thus, carry the risk of triggering autoimmunity. There are multiple unique regulatory mechanisms aimed at preventing accidental activation of nucleic acid-sensing TLRs. Recent structural studies revealed that different nucleic acid-sensing TLRs have specific modes of recognizing nucleic acids as ligands regulated by diverse regulation mechanism both at the receptor and ligand levels. This review summarizes structural knowledge on the ligand recognition and regulation mechanism by nucleic acid-sensing TLRs.