Many bacterial pathogens have acquired the capacity to attach to and/or replicate inside human cells by avoiding cell intrinsic innate immune pathways. The subversion of host cell signaling by pathogens frequently depends on the ability to transport virulence proteins, called effector proteins, into the infected cell via specialised protein secretion systems. We work on a range of virulence effectors from pathogenic bacteria that interfere with host innate immune signalling pathways and block inflammation and cell death. In this way effector proteins can be used as tools to understand the innate responses important for control of the pathogen. We recently defined EspL as a T3SS cysteine protease effector that degrades the signalling proteins, RIPK1 and RIPK3 in the RHIM domain thereby inhibiting necroptosis and inflammation. More recently, we have worked to identify host substrates of EspL homologues found in Shigella, termed OspD2 and OspD3, which are also cysteine proteases. Using the proteomic approach, ProteoMap, we discovered that both OspD2 and OspD3 targeted components of the type I and type III interferon signalling pathway and blocked type I interferon signalling. EspL from EPEC also had activity in this pathway. This suggests that type I and/or type III interferon induced proteins mediate host defense against Shigella and EPEC infection. The activities of EspL and its homologues define a new family of bacterial effector proteins found in a range of bacteria and reveal the mechanisms by which gastrointestinal pathogens directly target inflammatory and cell death signalling pathways.