Stress Response Meets Autonomous Immunity

Stress response contributes to autonomous immune responses. Many stresses including infection induce integrated stress response (ISR). ISR is mediated by a set of kinases PKR, PERK, HRI, and GCN2. Viral dsRNA activates PKR. Viral proteins are produced in the endoplasmic reticulum and may cause ER stress, which activates PERK. Infection also can cause iron deficiency sensed by HRI kinase and amino acid shortage sensed by GCN2. The arrest of translation caused by ISR inhibits viral replication and activates NFkB, a major regulator of immunity. Therefore, ISR acts as an immunodefense mechanism. Other stress responses that contribute to immune defense include unfolded protein response (UPR). UPR activates degradation of ERassociated mRNAs and proteins including viral ones. DNA damage response leads to NFkB activation, and so does oxidative stress through various mechanisms. The major stress response factor p53 has anti-viral activity. Autophagy activated by many stresses also plays a role in immunodefense by degrading intracellular pathogens.

Keywords: DNA damage response, ERAD, Homeostasis, Immune response, Integrated stress response, NLRP3 inflammasome, Nrf2, Oxidative stress, RIDD, Unfolded protein response, Xenophagy.