<i>Salmonella typhimurium</i> Induces Apoptosis in Human Monocyte‐Derived Macrophages

Zhou, Xin; Mantis, Nicholas J.; Zhang, Xiao Ru; Potoka, Douglas A.; Watkins, Simon C.; Ford, Henri R.

doi:10.1111/j.1348-0421.2000.tb02594.x

Cited by 14 publications

(9 citation statements)

References 39 publications

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“…It is unlikely that the differences observed were due to impaired infectivity, since the number of viable bacteria recovered per well after 30 min of infection was in the range of 1 ϫ 10 5 to 2 ϫ 10 5 for all strains tested. It has been demonstrated that S. enterica serovar Typhimurium is able to trigger apoptosis of infected macrophages (6,8,26,35,49,69). This process seems to play a key role also in elicitation of immune responses to Salmonella (67,69).…”

Section: Resultsmentioning

confidence: 99%

“…It has been demonstrated that S. enterica serovar Typhimurium is able to trigger apoptosis of infected macrophages (6,8,26,35,49,69). This process seems to play a key role also in elicitation of immune responses to Salmonella (67,69). Since the intracellular survival of the mutant strain was reduced only in macrophages, not within epithelial cells, we decided to assess whether the capacity of the serovar Typhi ⌬gaiA mutant to stimulate programmed cell death was also affected.…”

Section: Resultsmentioning

confidence: 99%

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Characterization of a Novel Intracellularly Activated Gene from Salmonella enterica Serovar Typhi

et al. 2002

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A Salmonella enterica serovar Typhi gene that is selectively up-regulated upon bacterial invasion of eukaryotic cells was characterized. The open reading frame encodes a 298-amino-acid hydrophobic polypeptide (30.8 kDa), which is predicted to be an integral membrane protein with nine membrane-spanning domains. The protein is closely related (87 to 94% reliability) to different transport and permease systems. Gene expression under laboratory conditions was relatively weak; however, sevenfold induction was observed in a high-osmolarity medium (300 mM NaCl). The growth pattern in a laboratory medium of a serovar Typhi strain Ty2 derivative containing a 735-bp in-frame deletion in this gene, named gaiA (for gene activated intracellularly), was not affected. In contrast, the mutant was partially impaired in intracellular survival in murine peritoneal macrophages, as well as in human monocyte-derived macrophages. However, in the case of human macrophages, this survival defect was modest and evident only at late infection times (24 h). Despite the distinct intracellular survival kinetics displayed in macrophages of different species, the gaiA null mutant was significantly affected in its potential to trigger apoptosis in both murine and human macrophages. Provision of the gaiA gene in trans resulted in complementation of these phenotypes. Interestingly, the absence of a functional gaiA gene caused a marked attenuation in the mouse mucin model, as shown by the increase (3 orders of magnitude) in the 50% lethal dose of the mutant strain over that of the parental strain Ty2 (P < 0.05). Altogether, these data indicate that the product encoded by the gaiA gene is required for triggering apoptosis and bacterial survival within murine macrophages, which is consistent with the in vivo results obtained in the mouse mucin model. However, gaiA was not required for initial intracellular survival in human cells, indicating that its role in the natural host might be more complex than is suggested by the studies performed in the murine system.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Characterization of a Novel Intracellularly Activated Gene from Salmonella enterica Serovar Typhi

et al. 2002

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“…The ability to survive inside macrophages is associated with host adaptation in mammals and birds (1,7,20,25). In mammalian species, the intracellular survival of Salmonella in macrophages eventually leads to killing of the host macrophage in an apoptosis-like way (3,4,10,12,14,18,23,27). The pigeon strains were found in smaller numbers in the pigeon peritoneal macrophages after 24 h than the porcine strains.…”

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confidence: 99%

Host Adaptation of Pigeon Isolates of Salmonella enterica subsp. enterica Serovar Typhimurium Variant Copenhagen Phage Type 99 Is Associated with Enhanced Macrophage Cytotoxicity

et al. 2003

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Phage type 99 of Salmonella enterica subsp. enterica serovar Typhimurium variant Copenhagen strains isolated from pigeons were examined for the presence of genotypic and phenotypic characteristics. The pulsedfield gel electrophoresis patterns obtained with XbaI and BlnI from 38 pigeon strains were compared with those obtained from 89 porcine, poultry, and human strains of variant Copenhagen. Identical patterns with XbaI and four closely related patterns with BlnI were obtained with the pigeon strains, whereas 16 XbaI patterns were found with the other strains. The XbaI patterns of the pigeon strains showed a low genetic similarity to the patterns of the porcine, poultry, and human strains and invariably showed a low-molecular-weight band that was absent in the majority of the other strains. The virulence genes shdA, spvR, pefA, sopE, and spvB were uniformly present in six pigeon isolates representing the genetic diversity found with BlnI. These six pigeonderived strains were highly cytotoxic for pigeon macrophages compared to three porcine strains. After experimental infection of pigeons with a pigeon strain, clinical symptoms, fecal shedding, and colonization of internal organs were more pronounced than those after infection with a porcine strain. These data suggest that the phage type 99 strains used in this study are highly adapted to pigeons and should be classified as a host-restricted lineage of the serovar Typhimurium.

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“…Some studies have shown that S. typhi and Salmonella enterica serovar Typhimurium (S. typhimurium) can mediate macrophage apoptosis. [6][7][8][9][10] The virulence of Salmonella strains in humans and other animals is frequently serovar specific. S. typhi causes typhoid fever only in humans, but no disease is associated with experimental infections in mice.…”

Section: Introductionmentioning

confidence: 99%

A Salmonella enterica serovar Typhi plasmid induces rapid and massive apoptosis in infected macrophages

et al. 2010

Cell Mol Immunol

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pR ST98 is a chimeric plasmid isolated from Salmonella enterica serovar Typhi (S. typhi) that mediates the functions of drug resistance and virulence. Previously, we reported that Salmonella plasmid virulence (spv) genes were present in S. typhi. In our current study, we investigated whether plasmid pR ST98 exhibits significant cytotoxicity in macrophages. pR ST98 was transferred into the avirulent Salmonella enterica serovar Typhimurium (S. typhimurium) strain RIA to create the transconjugant pR ST98 /RIA. The standard S. typhimurium virulent strain SR-11, which carries a 100-kb virulence plasmid, was used as a positive control. The bacterial strains were incubated with a murine macrophage-like cell line (J774A.1) in vitro. Apoptosis of J774A.1 cells was examined by electron microscopy and flow cytometry after annexin-V/propidium iodide labeling, and the survival of Salmonella strains in J774A.1 cells was determined. Results showed that macrophages infected with strain pR ST98 /RIA displayed greater levels of apoptosis than those infected with RIA and that pR ST98 may increase bacterial survival in macrophages. Further studies showed that the pR ST98 -induced death of macrophages was associated with the loss of mitochondrial membrane potential and that pR ST98 may activate caspase-9 and then caspase-3. The research data indicate that the virulence of bacteria that contain the pR ST98 plasmid is enhanced; the presence of this plasmid increases the survival of the bacterial pathogen and acts through the mitochondrial pathway to mediate macrophage apoptosis.

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Salmonella typhimurium Induces Apoptosis in Human Monocyte‐Derived Macrophages

Abstract: Salmonella species represent a leading cause of gastroenteritis worldwide.

Cited by 14 publications

References 39 publications

Characterization of a Novel Intracellularly Activated Gene from Salmonella enterica Serovar Typhi

Characterization of a Novel Intracellularly Activated Gene from Salmonella enterica Serovar Typhi

Host Adaptation of Pigeon Isolates of Salmonella enterica subsp. enterica Serovar Typhimurium Variant Copenhagen Phage Type 99 Is Associated with Enhanced Macrophage Cytotoxicity

A Salmonella enterica serovar Typhi plasmid induces rapid and massive apoptosis in infected macrophages

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