FIG. 10.

S. flexneri-induced macrophage death. Depending on the Mxi-Spa T3SS, S. flexneri enhances its uptake by macrophages and secretes the translocators/effectors IpaB and IpaC to escape from the phagosome. In the cytoplasm, the remaining bacterial pool of IpaB is gradually released. Secreted IpaB integrates into membranes in a cholesterol-dependent manner and triggers the proteolytic activation of procaspase-1, which might be further promoted by TPPII. Active caspase-1 executes cell death and cleaves the precursors of the proinflammatory cytokines IL-1β and IL-18. The mature cytokines are released from the dying macrophage and elicit the strong inflammation characteristic of shigellosis.