In vivo apoptosis in Shigella flexneri infections

Zychlinsky, Arturo; Thirumalai, Kavitha; Arondel, Josette; Cantey, J. Robert; Aliprantis, Antonios O.; Sansonetti, P

doi:10.1128/iai.64.12.5357-5365.1996

Cited by 163 publications

(74 citation statements)

References 27 publications

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“…74 A similar outcome occurs, at least in vitro, with Shigella-infected human monocyte-derived DC. 75 Large numbers of apoptotic phagocytic cells are observed both in the subepithelial dome in the rabbit intestinal model of shigellosis 76 and in colo-rectal biopsies of infected patients. 77 In addition to caspase-1, another endogenous protease, the cytoplasmic serine protease tripeptidyl peptidase II, a component of the apoptotic pathway located upstream of caspase-1, is involved in the apoptotic cascade elicited by Shigella.…”

Section: Escape From Phagocytic Vacuole and Induction Of Macrophage Amentioning

confidence: 99%

“…Indeed, apoptotic cell death, including macrophage, DC, T and B cells, in the lamina propria of infected patients is markedly upregulated at the acute stage of Shigella where an increased number of necrotic cells is also seen. 76,77,115 Phenotypic analysis of apoptotic cells revealed that about 40% of T cells underwent apoptosis. Induction of apoptosis at the local site in the early phase of infection is associated with a significant upregulation of Fas/Fas-L and perforin and granzyme A expression and a downregulation of Bcl-2 and IL-2, which promote cell survival.…”

Section: Impact Of Shigella-induced Modulation Of Host Innate Immunitmentioning

confidence: 99%

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Shigella’s ways of manipulating the host intestinal innate and adaptive immune system: a tool box for survival?

2007

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Shigella, a Gram-negative invasive enteropathogenic bacterium, causes the rupture, invasion and inflammatory destruction of the human colonic epithelium. This complex and aggressive process accounts for the symptoms of bacillary dysentery. The so-called invasive phenotype of Shigella is linked to expression of a type III secretory system (TTSS) injecting effector proteins into the epithelial cell membrane and cytoplasm, thereby inducing local but massive changes in the cell cytoskeleton that lead to bacterial internalization into non-phagocytic intestinal epithelial cells. The invasive phenotype also accounts for the potent proinflammatory capacity of the microorganism. Recent evidence indicates that a large part of the mucosal inflammation is initiated by intracellular sensing of bacterial peptidoglycan by cytosolic leucine-rich receptors of the NOD family, particularly NOD1, in epithelial cells. This causes activation of the nuclear factor kappa B and c-JunNH 2 -terminal-kinase pathways, with interleukin-8 appearing as a major chemokine mediating the inflammatory burst that is dominated by massive infiltration of the mucosa by polymorphonuclear leukocytes. Not unexpectedly, this inflammatory response, which is likely to be very harmful for the invading microbe, is regulated by the bacterium itself. A group of proteins encoded by Shigella, which are injected into target cells by the TTSS, has been recently recognized as a family of potent regulators of the innate immune response. These enzymes target key cellular functions that are essential in triggering the inflammatory response, and more generally defense responses of the intestinal mucosa. This review focuses on the mechanisms employed by Shigella to manipulate the host innate response in order to escape early bacterial killing, thus ensuring establishment of its infectious process. The escape strategies, the possible direct effect of Shigella on B and T lymphocytes, their impact on the development of adaptive immunity, and how they may help explain the limited protection induced by natural infection are discussed.

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Section: Escape From Phagocytic Vacuole and Induction Of Macrophage Amentioning

confidence: 99%

Section: Impact Of Shigella-induced Modulation Of Host Innate Immunitmentioning

confidence: 99%

Shigella’s ways of manipulating the host intestinal innate and adaptive immune system: a tool box for survival?

2007

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“…Nevertheless, these model systems all require the presence of one or more foreign proteins produced on the surface of the pathogen to achieve actin-based motility. In addition these pathogens stimulate apoptosis [Bair et al, 1996;Rogers et al, 1996;Zychlinsky et al, 1996]. These considerations point to the need for an intact cell model system that avoids pathogen-derived proteins and pathogen-induced apoptosis.…”

Section: Introductionmentioning

confidence: 99%

Actin‐based endosome and phagosome rocketing in macrophages: activation by the secretagogue antagonists lanthanum and zinc

Southwick

Zhang

et al. 2002

Cell Motil. Cytoskeleton

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Although motile endocytic vesicles form actin-rich rocket tails [Merrifield et al., 1999: Nature Cell Biol 1:72-74], the mechanism of intracellular organelle locomotion remains poorly understood. We now demonstrate that bone marrow macrophages treated with lanthanum and zinc ions, well-known secretagogue antagonists, reliably exhibit vesicle motility. This treatment results in accentuated membrane ruffling and the formation of phagosomes and early endosomes that move rapidly through the cytoplasm by assembling actin filament rocket tails. Protein-specific immunolocalization demonstrated the presence of Arp2/3 complex in the polymerization zone and throughout the actin-rich tail, whereas N-WASP was most abundant in the polymerization zone. Although Arp2/3 and N-WASP play essential roles in nucleating filament assembly, other processes (i.e., elongation and filament cross-linking) are required to produce forces needed for motility. Efficient elongation was found to require zyxin, VASP, and profilin, proteins that interact by means of their ABM-1 and ABM-2 proline-rich motifs. The functional significance of these motifs was demonstrated by inhibition of vesicle motility by the motif-specific ABM-1 and ABM-2 analogues. Furthermore, lanthanum/zinc treatment also facilitated the early onset of actin-based vaccinia motility, a process that also utilizes Arp2/3 and N-WASP for nucleation and the zyxin-VASP-profilin complex for efficient elongation. Although earlier studies using cell extracts clouded the role of oligoproline sequences in activating the polymerization zone, our studies emphasize the importance of evaluating motility in living cells.

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“…It is well known that many pathogenic bacteria (e.g. Staphylococcus aureus, Salmonella typhimurium and Shigella flexneri) induce apoptotic cell death (Lindgren et al 1996;Monack et al 1996;Zychlinsky et al 1996;Menzies and Kourteva 1998;Nuzzo et al 2000). It has been shown that the induction of apoptosis by ingested Sh.…”

Section: Discussionmentioning

confidence: 99%

Invasive phenotype and apoptosis induction of Plesiomonas shigelloides P-1 strain to Caco-2 cells

et al. 2005

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Aims: The mechanism of the host cell invasion of Plesiomonas shigelloides and its capability to induce apoptosis were investigated. Methods and Results: We performed a time course experiment on the bacterial adherence and invasion of the P. shigelloides P-1 strain into Caco-2 cells using an invasion assay and flow cytometry. The adherence of P. shigelloides to the Caco-2 cells was almost completed within 10 min after the infection. Thereafter, P. shigelloides starts internalization within the Caco-2 cells, which was completed within 60 min after the infection. Based on the invasion assay using nocodazole, cytochalasin D, and genistein, it became clear that the mechanism of the internalization depended on the signal transduction followed by the rearrangement of the cytoskeletal protein. Based on the DNA laddering and TUNEL methods, the cytotoxicity of the Caco-2 cells by the invasion of P. shigelloides occurred through the induction of apoptosis. Conclusions: This work demonstrated that the mechanism of invasion of P. shigelloides into Caco-2 cells and the invasion of P. shigelloides induces apoptotic cell death. Significance and Impact of the Study: This work revealed the virulence factor, which may be important for understanding of the pathogenesis of P. shigelloides.

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In vivo apoptosis in Shigella flexneri infections

Cited by 163 publications

References 27 publications

Shigella’s ways of manipulating the host intestinal innate and adaptive immune system: a tool box for survival?

Shigella’s ways of manipulating the host intestinal innate and adaptive immune system: a tool box for survival?

Actin‐based endosome and phagosome rocketing in macrophages: activation by the secretagogue antagonists lanthanum and zinc

Invasive phenotype and apoptosis induction of Plesiomonas shigelloides P-1 strain to Caco-2 cells

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