RRC ID 1139
Author Suzuki T, Nakanishi K, Tsutsui H, Iwai H, Akira S, Inohara N, Chamaillard M, Nuñez G, Sasakawa C.
Title A novel caspase-1/toll-like receptor 4-independent pathway of cell death induced by cytosolic Shigella in infected macrophages.
Journal J. Biol. Chem.
Abstract Shigella-induced macrophage cell death is an important step in the induction of acute inflammatory responses that ultimately lead to bacillary dysentery. Cell death was previously reported to be dependent upon the activation of caspase-1 via interaction with IpaB secreted by intracellular Shigella, but in this study, we show that Shigella infection of macrophages can also induce cell death independent of caspase-1 or IpaB activity. Time-lapse imaging and electron microscopic analyses indicated that caspase-1-dependent and -independent cell death is morphologically indistinguishable and that both resemble necrosis. Analyses of Shigella mutants or Escherichia coli using co-infection with Listeria suggested that a component common to Gram-negative bacteria is involved in inducing caspase-1-independent cell death. Further studies revealed that translocation of bacterial lipid A into the cytosol of macrophages potentially mediates cell death. Notably, cell death induced by cytosolic bacteria was TLR4-independent. These results identify a novel cell death pathway induced by intracellular Gram-negative bacteria that may play a role in microbial-host interactions and inflammatory responses.
Volume 280(14)
Pages 14042-50
Published 2005-4-8
DOI 10.1074/jbc.M414671200
PII M414671200
PMID 15695506
MeSH Animals Bone Marrow Cells / cytology Bone Marrow Cells / metabolism Bone Marrow Cells / microbiology Caspase 1 / genetics Caspase 1 / metabolism* Cell Death / physiology* Cells, Cultured Dendritic Cells / cytology Dendritic Cells / metabolism Dendritic Cells / microbiology Enzyme Activation Humans Lipid A / metabolism Macrophages / cytology Macrophages / metabolism* Macrophages / microbiology Mice Mice, Inbred C57BL Receptors, Immunologic / genetics Receptors, Immunologic / metabolism* Shigella flexneri / metabolism* Shigella flexneri / pathogenicity* Toll-Like Receptor 4
IF 4.106
Times Cited 47
Pathogenic microorganisms IID 671 IID 506