Cytosolic Nucleic Acid Sensors in Inflammatory and Autoimmune Disorders

Abstract

Innate immunity employs germline-encoded pattern recognition receptors (PRRs) to sense microbial pattern molecules. Recognition of pathogen-associated molecular patterns (PAMPs) by various PPRs located on the cell membrane or in the cytosol leads to the activation of cell signaling pathways and production of inflammatory mediators. Nucleic acids including DNA, RNA, and their derivatives are potent PAMPs which can be recognized by multiple PRRs to induce inflammatory responses. While nucleic acid sensors can also sense endogenous nucleic acids, they are capable of discriminating self from non-self. However, defects in nucleic acid sensing PRRs or dysregulation of nucleic acid sensing signaling pathways may cause excessive activation of the immune system resulting in the development of inflammatory and autoimmune diseases. This review will discuss the major pathways for sensing intracellular nucleic acids and how defects in these nucleic acid sensing are associated with different kinds of autoimmune and inflammatory disorders.

Keywords: AIM2; Autoimmune diseases; Cytosolic pattern recognition receptors; Inflammatory diseases; Nucleic acid sensors; RIG-I; STING; cGAS.