IPAB, A SHIGELLA-FLEXNERI INVASIN, COLOCALIZES WITH INTERLEUKIN-1-BETA-CONVERTING ENZYME IN THE CYTOPLASM OF MACROPHAGES

Shigellae are the most prevalent etiological agents of dysentery, A cr ucial step in shigella pathogenesis is the induction of macrophage apo ptosis. The invasion plasmid antigen B (IpaB) is necessary and suffici ent to induce macrophage programmed cell death. IpaB activates apoptos is by binding to interleukin-1 beta (IL-1 beta)-converting enzyme (ICE ) or a highly homologous protease, Here, we show that IpaB is dissemin ated throughout the cytoplasm of shigella-infected macrophages as dete cted by both immunofluorescence and immunoelectron microscopy, The cyt oplasmic distribution of IpaB requires phagosome escape, and it is spe cific to IpaB, since lipopolysaccharide, used here as a bacterial mark er, remains closely associated with the bacteria, In double labeling e xperiments, we show that IpaB and ICE colocalize in the cytoplasm of t he macrophage, suggesting that soon after secretion, IpaB binds to ICE to initiate apoptosis and to promote the cleavage of IL-1 beta.