CASP4 and infection: For both species, cell death was predominantly dependent on GSDMD and caspase-1, indicating the canonical inflammasome pathway is induced by Shigella. There may be a minor contribution to cell death for the noncanonical pathway, since immunoblots indicated that caspase-4 was activated by infection by both S. sonnei and S. flexneri and that caspase-4 deficiency or NLRP3 inhibition led to less pyroptosis over time than control cells.