Toll-like receptors (TLRs) play an important role in innate immune responses against pathogenic microorganisms or tissue damage. Nucleic acid (NA)-sensing TLRs localize in intracellular vesicular compartments and recognize foreign-derived and host-derived nucleic acid ligands. Inappropriate activation of NA-sensing TLRs can cause pathogenic inflammation and autoimmunity. Multiple regulatory mechanisms exist to limit recognition of self-NAs. This review summarizes recent progress that has been made in understanding how NA-sensing TLRs are regulated via trafficking, proteolytic cleavage, as well as ligand processing and recognition.
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