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. For example, we recently discovered that enteropathogenic E. coli (EPEC), uses the bacterial T3SS effector, EspL to block RHIM-containing protein mediated inflammatory and necroptotic signalling. EspL was defined as a novel cysteine protease that degrades the signalling proteins, RIPK1, RIPK3, TRIF and ZBP1/DAI in the RHIM domain. More recently, we have been identifying 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 effectors targeted components of the type I interferon signalling pathway. This suggests that Shigella activity blocks the host type I interferon response and that type I interferon induced proteins mediate host defense against Shigella 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.