title: IpaB, a Shigella flexneri invasin, colocalizes with interleukin-1 beta-converting enzyme in the cytoplasm of macrophages.
abstract: Shigellae are the most prevalent etiological agents of dysentery. A crucial step in shigella pathogenesis is the induction of macrophage apoptosis. The invasion plasmid antigen B (IpaB) is necessary and sufficient to induce macrophage programmed cell death. IpaB activates apoptosis by binding to interleukin-1 beta (IL-1 beta)-converting enzyme (ICE) or a highly homologous protease. Here, we show that IpaB is disseminated throughout the cytoplasm of shigella-infected macrophages as detected by both immunofluorescence and immunoelectron microscopy. The cytoplasmic distribution of IpaB requires phagosome escape, and it is specific to IpaB, since lipopolysaccharide, used here as a bacterial marker, remains closely associated with the bacteria. In double-labeling experiments, we show that IpaB and ICE colocalize in the cytoplasm of the macrophage, suggesting that soon after secretion, IpaB binds to ICE to initiate apoptosis and to promote the cleavage of IL-1 beta.
authors.affiliation: The Skirball Institute, New York University School of Medicine, New York 10016, USA.
authors.forename: K
authors.initials: K
authors.lastname: Thirumalai
authors.forename: K S
authors.initials: KS
authors.lastname: Kim
authors.forename: A
authors.initials: A
authors.lastname: Zychlinsky
mesh_terms: D018829:Adhesins, Bacterial; D000818:Animals; D001426:Bacterial Proteins / Q000378:metabolism* / Q000648:ultrastructure; D020170:Caspase 1; D003546:Cysteine Endopeptidases / Q000378:metabolism*; D003593:Cytoplasm / Q000201:enzymology* / Q000378:metabolism*; D006801:Humans; D007375:Interleukin-1 / Q000378:metabolism*; D008264:Macrophages / Q000201:enzymology / Q000378:metabolism* / Q000648:ultrastructure; D016253:Microscopy, Immunoelectron; D012763:Shigella flexneri / Q000378:metabolism* / Q000472:pathogenicity / Q000648:ultrastructure; D013347:Subcellular Fractions / Q000378:metabolism
chemical_list: D018829:Adhesins, Bacterial; D001426:Bacterial Proteins; D007375:Interleukin-1; C053476:invasin, Yersinia; C087447:ipaB protein, Shigella; D003546:Cysteine Endopeptidases; D020170:Caspase 1