Intracellular inflammatory sensors for foreign invaders and substances of self-origin

In order to survive, all organisms must recognize and eliminate foreign invaders such as infectious pathogens, chemicals, ultraviolet rays, metabolites and damaged or transformed self-tissues, as well as allogenic organs in cases of transplantation. Recent research in innate immunity has elucidated that there are versatile inflammatory sensors on spatiotemporal 'sentry duty' that recognize substances derived from both 'nonself' and 'self', e.g., Toll-like receptors, retinoic acid-inducible gene-I-like receptors, nucleotide oligomerization domain-like receptors and c-type lectin receptors. Having acquired high-level functions through the development of multiple molecules, higher organisms have established both extracellular and intracellular sensors that can discriminate danger-associated molecular patterns from promiscuous, but biologically similar, molecular patterns. In addition, 'loss-of-function' or 'gain-of-function' mutations in these inflammatory sensors have been linked (at least in part) with the etiology and severity of autoimmune diseases, autoinflammatory diseases and immunocompromised diseases in humans. Further studies focusing on the role of these inflammatory sensors in the development of immune disorders would highlight new avenues for the development of novel diagnostic and therapeutic applications with regard to these diseases.