Helicobacter pylori induces β3GnT5 in human gastric cell lines, modulating expression of the SabA ligand sialyl–Lewis x

Marcos, Nuno T.; Magalhães, Ana; Ferreira, Bibiana I.; Oliveira, Maria José; Carvalho, Ana Sofía; Mendes, Nuno; Gilmartin, Tim; Head, Steven R.; Figueiredo, Céu; David, Leonor; Santos-Silva, Filipe; Reis, Celso A.

doi:10.1172/jci34324

Cited by 86 publications

(113 citation statements)

References 51 publications

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“…Both cancer and infection can lead to altered glycosylation of cellular proteins (26)(27)(28). There are undoubtedly several explanations for this; it is likely that a part of the changes in cellular glycosylation patterns may be associated with altered expression of NKG2D ligands, possibly caused by an evolutionary pressure to limit immune recognition.…”

Section: Discussionmentioning

confidence: 99%

“…However, many proteins that are normally glycosylated show no loss of function when glycosylation is prevented (24), suggesting that additional processes can act in parallel. Cancer and infection often result in altered glycosylation of cellular proteins (26)(27)(28). Although the purpose may be numerous, it is likely that changes in glycosylation participate in escaping immune recognition.…”

mentioning

confidence: 99%

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2-Deoxy d-Glucose Prevents Cell Surface Expression of NKG2D Ligands through Inhibition of N-Linked Glycosylation

Andresen

Skovbakke

Persson

et al. 2012

The Journal of Immunology

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NKG2D ligand surface expression is important for immune recognition of stressed and neotransformed cells. In this study, we show that surface expression of MICA/B and other NKG2D ligands is dependent on N-linked glycosylation. The inhibitor of glycolysis and N-linked glycosylation, 2-deoxy-d-glucose (2DG), potently inhibited surface expression of MICA/B after histone deacetylase inhibitor treatment; the inhibition occurred posttranscriptionally without affecting MICA promoter activity. Transient overexpression of MICA surface expression was also inhibited by 2DG. 2DG blocks N-linked glycosylation of MICA/B by a reversible mechanism that can be alleviated by addition of d-mannose; this does not, however, affect the inhibition of glycolysis. Addition of d-mannose restored MICA/B surface expression after 2DG treatment. In addition, specific pharmacological or small interfering RNA-mediated targeting of glycolytic enzymes did not affect MICA/B surface expression, strongly suggesting that N-linked glycosylation, and not glycolysis, is essential for MICA/B surface expression. Corroborating this, tunicamycin, a selective inhibitor of N-linked glycosylation, abolished MICA/B surface expression without compromising activation of MICA promoter activity. NK cell-mediated killing assay and staining with a recombinant NKG2D–Fc fusion protein showed that all functional NKG2D ligands induced by histone deacetylase inhibitor treatment were abolished by 2DG treatment and fully reconstituted by further addition of d-mannose. Our data suggest that posttranslational N-linked glycosylation is strictly required for NKG2D ligand surface expression. Cancer and infection often result in aberrant glycosylation, which could likely be involved in modulation of NKG2D ligand expression. Our data further imply that chemotherapeutic use of 2DG may restrict NKG2D ligand surface expression and inhibit secretion of immunoinhibitory soluble NKG2D ligands.

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

2-Deoxy d-Glucose Prevents Cell Surface Expression of NKG2D Ligands through Inhibition of N-Linked Glycosylation

Andresen

Skovbakke

Persson

et al. 2012

The Journal of Immunology

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“…Thus, we hypothesized that L-fucose plays a similar role in the interaction between H. pylori and gastric epithelial cells. A recent study showed that H. pylori induced host cells to overexpress ␤1,3-N-acetylglucosaminyltransferase (␤3GnT5), which indirectly produced more sialyl Le x (21), suggesting that the pathogen may induce the host to manufacture specific glycans and to activate transcription of several genes simultaneously.…”

mentioning

confidence: 99%

Role for α- l -fucosidase in the control of Helicobacter pylori -infected gastric cancer cells

Liu

Huang

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

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Infecting about one-half of the global human population, Helicobacter pylori is well established as the primary cause of gastritis, duodenal ulcer, and gastric cancer. Currently there is no clear information regarding if and how host cells interact with H. pylori, and if such interactions are dependent on the type of gastric disease. Using fluorescently labeled fucose-containing glycoconjugates, we provide evidence observing both the uptake of L-fucose from gastric cancer cells to H. pylori and that human ␣-L-fucosidase 2 (FUCA2) is secreted only under coculture conditions (i.e., host cells infected with H. pylori). Upon depletion of FUCA2 by RNA interference and detection of translocated CagA (a virulence factor of H. pylori) in host cells, FUCA2 was found to be essential for H. pylori adhesion, in particular to the gastric cancer-and duodenal ulcer-specific strains. Additionally FUCA2 was shown to significantly enhance the expression of Lewis x antigen in H. pylori, which is critical for bacterial cell adhesion in the pathogenesis and defense strategy to escape host surveillance. These findings not only demonstrate an important connection between FUCA2 and the adhesion, growth, and pathogenicity of H. pylori, but also support the idea that FUCA2 is a potential target for clinical diagnosis and therapeutic intervention of H. pylori-related diseases.

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“…The H. pylori glycan receptors include fucosylated ABO blood group antigens [7,8], glycans with charged groups, such as sialic acid [9] or sulfate [10], and neolacto core chains [11] Figure 1) [9,12]. We have demonstrated in vitro that H. pylori is able to upregulate the bio synthesis of the sialyl-Lewis x structure by modulating the expression of b3GnT5 and thus increasing the bacteria's capacity to adhere to epithelial cells [13]. The BabA and SabA adhesins are better characterized regarding their receptor specificity but the spectrum of H. pylori adhesin-receptor interactions is vast and further studies are needed to identify novel targets of the bacterial adhesins.…”

Section: Helicobacter Pylori: Specialized In the Colonization Of The mentioning

confidence: 91%

Sweet receptors mediate the adhesion of the gastric pathogenHelicobacter pylori: glycoproteomic strategies

Magalhães

Ismail

Reis³

2010

Expert Review of Proteomics

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Helicobacter pylori induces β3GnT5 in human gastric cell lines, modulating expression of the SabA ligand sialyl–Lewis x

Cited by 86 publications

References 51 publications

2-Deoxy d-Glucose Prevents Cell Surface Expression of NKG2D Ligands through Inhibition of N-Linked Glycosylation

2-Deoxy d-Glucose Prevents Cell Surface Expression of NKG2D Ligands through Inhibition of N-Linked Glycosylation

Role for α- l -fucosidase in the control of Helicobacter pylori -infected gastric cancer cells

Sweet receptors mediate the adhesion of the gastric pathogenHelicobacter pylori: glycoproteomic strategies

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