PloS one, 2013-12, Vol.8 (12), p.e78191-e78191
2013
Details
- Autor(en) / Beteiligte
- Titel
- Helicobacter pylori cholesteryl α-glucosides contribute to its pathogenicity and immune response by natural killer T cells
- Ist Teil von
- PloS one, 2013-12, Vol.8 (12), p.e78191-e78191
- Ort / Verlag
- United States: Public Library of Science
- Erscheinungsjahr
- 2013
- Link zum Volltext
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- Approximately 10-15% of individuals infected with Helicobacter pylori will develop ulcer disease (gastric or duodenal ulcer), while most people infected with H. pylori will be asymptomatic. The majority of infected individuals remain asymptomatic partly due to the inhibition of synthesis of cholesteryl α-glucosides in H. pylori cell wall by α1,4-GlcNAc-capped mucin O-glycans, which are expressed in the deeper portion of gastric mucosa. However, it has not been determined how cholesteryl α-glucosyltransferase (αCgT), which forms cholesteryl α-glucosides, functions in the pathogenesis of H. pylori infection. Here, we show that the activity of αCgT from H. pylori clinical isolates is highly correlated with the degree of gastric atrophy. We investigated the role of cholesteryl α-glucosides in various aspects of the immune response. Phagocytosis and activation of dendritic cells were observed at similar degrees in the presence of wild-type H. pylori or variants harboring mutant forms of αCgT showing a range of enzymatic activity. However, cholesteryl α-glucosides were recognized by invariant natural killer T (iNKT) cells, eliciting an immune response in vitro and in vivo. Following inoculation of H. pylori harboring highly active αCgT into iNKT cell-deficient (Jα18(-/-)) or wild-type mice, bacterial recovery significantly increased in Jα18(-/-) compared to wild-type mice. Moreover, cytokine production characteristic of Th1 and Th2 cells dramatically decreased in Jα18(-/-) compared to wild-type mice. These findings demonstrate that cholesteryl α-glucosides play critical roles in H. pylori-mediated gastric inflammation and precancerous atrophic gastritis.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 1932-6203eISSN: 1932-6203DOI: 10.1371/journal.pone.0078191Titel-ID: cdi_plos_journals_1463094877
- Format
- –
- Schlagworte
- Adolescent, Adult, Aged, Aged, 80 and over, Animals, Antigens, Atrophy, Bacteria, Biochemistry, Biophysics, Cancer, Cell activation, Cell walls, Child, Clinical isolates, Dendritic cells, Enzymatic activity, Female, Gastric mucosa, Gastritis, Gastritis, Atrophic - genetics, Gastritis, Atrophic - immunology, Gastritis, Atrophic - microbiology, Gastritis, Atrophic - pathology, Glucosides, Glucosides - immunology, Glucosyltransferase, Helicobacter Infections - genetics, Helicobacter Infections - immunology, Helicobacter Infections - pathology, Helicobacter pylori, Helicobacter pylori - genetics, Helicobacter pylori - immunology, Helicobacter pylori - pathogenicity, Helper cells, Humans, Immune response, Immune system, Immunology, Infections, Inflammation, Inflammatory bowel disease, Inoculation, Lymphocytes, Lymphocytes T, Lymphoma, Male, Medical research, Mice, Mice, Knockout, Middle Aged, Mucin, Natural killer cells, Natural Killer T-Cells - immunology, Natural Killer T-Cells - pathology, Neurosciences, Pathogenesis, Pathogenicity, Pathogens, Pathology, Phagocytosis, Phagocytosis - immunology, Polysaccharides, Science, Stem cells, Stomach, T cell receptors, Th1 Cells - immunology, Th1 Cells - pathology, Th2 Cells - immunology, Th2 Cells - pathology, Tumor necrosis factor-TNF, University graduates