Model of apoptosis inhibition by Shigella flexneri at multiple checkpoints in epithelial cells. Infection of epithelial cells by S. flexneri results in several levels of protection from apoptosis. First, the bacteria prevent cytochrome c release from the mitochondria through the upregulation of BCL-2 proteins. Second, the extrinsic pathway of apoptosis is inhibited from in vivo stimuli such as TNF-α and FasL. This inhibition is most likely due to the upregulation of proteins like CFLAR, TNFAIP3, TNFAIP8, and FAIM3. Third, infection leads to the induced expression of JUN and NF-κB, which has many pro-survival effects including the increased expression of the IAPs (BIRC4, BIRC1, BIRC5, and BIRC7), the Bcl-2 family, and caspase-8 inhibitors. Finally, the bacteria prevent caspase-3 activation to provide downstream protection in the presence of strong apoptosis inducers. Through the use of T3SS effector proteins, the bacteria could directly generate mitochondrial protection, the inhibition of the extrinsic pathway, and caspase-3 inhibition. Alternatively, S. flexneri could indirectly produce these changes through the upregulation of pro-survival factors like JUN and NF-κB.