Fig. 4.

Bacteria influence the immune response to manipulate pyroptosis. Shigella flexneri inhibits caspase-4/11 through the secreted effector protein OspC3 to mediate arginine ADP-riboxanation and block the maturation of caspase-4/11 and consequently GSDMD cleavage. Yersinia secretes YopJ to inhibit TAK1, further activating RIPK1/caspase-8-dependent pyroptosis. Simultaneously, YopJ binds to RIPK1 to function on the Rag-Ragulator complex, causing cleavage and partial activation of GSDMD by caspase-1/11 and cleavage of GSDME by caspase-3/7. Mycobacteria secrete EST12, which binds to RACK1, recruiting UCHL5 to promote deubiquitination of NLRP3 and thus inducing NLRP3 and GSDMD to trigger pyroptosis. Additionally, Brd4 regulates the activation of the NAIP-NLRC4 inflammasome by recruiting PU.1 and IRF8 to initiate the maturation of caspase-1 and activate caspase-8 to cause IEC in cells infected by Salmonella