Regulation of the innate immune system by ubiquitin and ubiquitin-like modifiers

Detection of invading pathogens by pattern recognition receptors (PRRs) is crucial for the activation of the innate immune response. These sensors signal through intertwining signaling cascades which result in the expression of pro-inflammatory cytokines and type I interferons. Conjugation, or binding, of ubiquitin and ubiquitin-like modifiers (UBLs) to a plethora of immune signaling molecules forms a common theme in innate immune regulation. Numerous E3 ligases and deubiquitylating enzymes (DUBs) actively modify signaling components in order to achieve a balanced activation of the innate immune system. This review will discuss how this balance is achieved and which questions remain regarding innate immune regulation by ubiquitin and UBLs.