Autophagic checks and balances of cellular immune responses

IRF3 (interferon regulatory factor 3) is a critical component of the antiviral innate immune response. IRF3 deficiency causes detrimental effects to the host during virus infection. Dysregulation of IRF3 functions is associated with viral, inflammatory, and hepatic diseases. Both transcriptional and pro-apoptotic activities of IRF3 are involved in the exacerbated inflammation and apoptosis in liver injury induced by ethanol and high-fat diets. Therefore, regulation of IRF3 activities has consequences, and it is a potential therapeutic target for infectious and inflammatory diseases. We recently revealed that IRF3 is degraded by a small molecule, auranofin, by activating the cellular macroautophagy/autophagy pathway. Autophagy is a catabolic pathway that contributes to cellular homeostasis and antiviral host defense. Degradation of IRF3 by autophagy may be a novel strategy used by the viruses to their benefit. In addition, IRF3 functions are harmful in other diseases, including liver injury and bacterial infection. A better understanding of the role of autophagy in regulating IRF3 functions has significant implications in developing therapeutic strategies. Therefore, autophagy provides checks and balances in the innate immune response.