IFIH1 and Autoimmunity: We contend that MDA5 signaling and associated ISG induction can be modulated to a set-point previously considered a flagrant emergency response or disease state, and that further study may reveal the mechanisms that permit RdRP mice to tolerate sustained MDA5-MAVS-mediated, highly augmented pathogen defenses without destructive autoimmunity or other chronic inflammatory sequelae.