<i>Helicobacter pylori</i>Induces Apoptosis of Macrophages in Association with Alterations in the Mitochondrial Pathway

Menaker, Rena J.; Ceponis, Peter J. M.; Jones, Nicola L.

doi:10.1128/iai.72.5.2889-2898.2004

Cited by 80 publications

(62 citation statements)

References 77 publications

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“…4). Additionally, H. pylori infection may escape from phagocytosis by an active method that causes macrophages to undergo apoptosis (11,12,18,49). These findings suggest that H. pylori develops strategies to escape from the immune defenses of IFN-g and macrophages, and the presence of high levels of IFN-g may pathologically affect gastric inflammation.…”

Section: Discussionmentioning

confidence: 88%

Helicobacter pylori Infection Activates Src Homology-2 Domain–Containing Phosphatase 2 To Suppress IFN-γ Signaling

Wang

Chen

Sheu

et al. 2014

The Journal of Immunology

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Helicobacter pylori infection not only induces gastric inflammation but also increases the risk of gastric tumorigenesis. IFN-γ has antimicrobial effects; however, H. pylori infection elevates IFN-γ–mediated gastric inflammation and may suppress IFN-γ signaling as a strategy to avoid immune destruction through an as-yet-unknown mechanism. This study was aimed at investigating the mechanism of H. pylori–induced IFN-γ resistance. Postinfection of viable H. pylori decreased IFN-γ–activated signal transducers and activators of transcription 1 and IFN regulatory factor 1 not only in human gastric epithelial MKN45 and AZ-521 but also in human monocytic U937 cells. H. pylori caused an increase in the C-terminal tyrosine phosphorylation of Src homology-2 domain–containing phosphatase (SHP) 2. Pharmacologically and genetically inhibiting SHP2 reversed H. pylori–induced IFN-γ resistance. In contrast to a clinically isolated H. pylori strain HP238, the cytotoxin-associated gene A (CagA) isogenic mutant strain HP238CagAm failed to induce IFN-γ resistance, indicating that CagA regulates this effect. Notably, HP238 and HP238CagAm differently caused SHP2 phosphorylation; however, imaging and biochemical analyses demonstrated CagA-mediated membrane-associated binding with phosphorylated SHP2. CagA-independent generation of reactive oxygen species (ROS) contributed to H. pylori–induced SHP2 phosphorylation; however, ROS/SHP2 mediated IFN-γ resistance in a CagA-regulated manner. This finding not only provides an alternative mechanism for how CagA and ROS coregulate SHP2 activation but may also explain their roles in H. pylori–induced IFN-γ resistance.

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Section: Discussionmentioning

confidence: 88%

Helicobacter pylori Infection Activates Src Homology-2 Domain–Containing Phosphatase 2 To Suppress IFN-γ Signaling

Wang

Chen

Sheu

et al. 2014

The Journal of Immunology

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“…Previous studies have demonstrated that infection of H. pylori induces cell apoptosis by Vac A protein (de Freitas et al, 2004;Galgani et al, 2004;Menaker et al, 2004;Cho et al, 2003;Fischer et al, 2004) and Cag A (Isomoto et al, 2010;Maeda and Mentis, 2007). Our previous studies showed the presence of M. hyorhinis and M. fermentans in fresh gastric cancer samples, but whether the infection of these mycoplasmas could directly induce gastric cells apoptosis, ulcer or cancer is unknown.…”

Section: Discussionmentioning

confidence: 99%

Mycoplasma hyorhinis and Mycoplasma fermentans induce cell apoptosis and changes in gene expression profiles of 32D cells

Liu

Shou

2011

Biol. Res.

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Infection of mycoplasmas has been linked to various human diseases including arthritis, pneumonia, infertility and cancer. While Mycoplasma hyorhinis and Mycoplasma fermentans have been detected in gastric adenocarcinomas, the mechanisms underlyine the pathogenesis are unknown. In this study, cell growth kinetics, Hoechst 33258 staining, DNA ladder assays, Western blotting analysis and cDNA microarray assays were performed to investigate the roles of M. hyorhinis and M. fermentans during infection of mammalian cells. Our data demonstrated that these mycoplasmas inhibid the growth of immortalised cell lines (32D and COS-7) ane tumor cell lines (HeLa and AGS). In addition, the infection of the 32D cell line with M. hyorhinis and M. fermentans induced compression of the nucleus, degradation of the cell genome and dysregulation of the expression of genes related to proliferation, apoptosis, tumorigenesis, signaling pathway and metabolism. Apoptosis related proteins Bcl-2, Bid and p53 were down-regulated, Fas was up-regulated and Bax was dysregulated in mycoplasma-infected 32D cells. Together, our data demonstrated that infection of mycoplasmas inhibitd cele growts through modifi cation of gene expression profi les and post-translation modifi cation of proliferation and apoptosis related proteins.

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“…Several other infectious organisms also induce apoptosis of host cells, including Mycobacterium tuberculosis (55)(56)(57), Crytosporidium parvum (58), Shigella flexneri (59), and Helicobacter pylori (60,61). Similar to Pneumocystis, these microorganisms also cause apoptosis through the intrinsic apoptosis pathway.…”

Section: Discussionmentioning

confidence: 99%

Suppression of Alveolar Macrophage Apoptosis Prolongs Survival of Rats and Mice withPneumocystisPneumonia

Lasbury

Durant

Ray

et al. 2006

The Journal of Immunology

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The number of alveolar macrophages is decreased in patients or animals with Pneumocystis pneumonia (Pcp). This loss of alveolar macrophages is in part due to apoptosis caused by Pneumocystis infection. The mechanism of apoptosis induction is unknown. Cell-free bronchoalveolar lavage fluids from Pneumocystis-infected rats or mice have the ability to induce apoptosis in normal alveolar macrophages. To characterize the mechanisms by which apoptosis proceeds in alveolar macrophages during Pcp, specific caspase inhibitors are tested for their ability to suppress the apoptosis. In vitro induction of apoptosis can be inhibited by the caspase-9 inhibitor (Z-LEHD-FMK) but not by the inhibitor to caspase-8 or -10. The caspase-9 inhibitor can also inhibit apoptosis of alveolar macrophages in vivo when it is intranasally instilled into dexamethasone-immunosuppressed, Pneumocystis-infected rats or L3T4 cell-depleted, Pneumocystis-infected mice. The number of alveolar macrophages rebounds in caspase-9 inhibitor-treated Pcp animals. Phagocytic activity of alveolar macrophages in treated animals is also recovered, and organism burden in these animals is reduced. Administration of caspase-9 inhibitor also clears the exudate that normally fills the alveoli during Pcp and decreases lung inflammation. Furthermore, caspase-9-treated Pcp animals survive for the entire 70-day period of the study, whereas nontreated Pcp animals die 40–60 days after initiation of infection. Depletion of recovered alveolar macrophages by intranasal administration of clodronate-containing liposomes in caspase-9 inhibitor-treated animals abrogates the effects of the inhibitor. Together, these results indicate that immunomodulation of the host response may be an alternative to current treatments for Pcp.

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Helicobacter pyloriInduces Apoptosis of Macrophages in Association with Alterations in the Mitochondrial Pathway

Cited by 80 publications

References 77 publications

Helicobacter pylori Infection Activates Src Homology-2 Domain–Containing Phosphatase 2 To Suppress IFN-γ Signaling

Helicobacter pylori Infection Activates Src Homology-2 Domain–Containing Phosphatase 2 To Suppress IFN-γ Signaling

Mycoplasma hyorhinis and Mycoplasma fermentans induce cell apoptosis and changes in gene expression profiles of 32D cells

Suppression of Alveolar Macrophage Apoptosis Prolongs Survival of Rats and Mice withPneumocystisPneumonia

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