Intracellular Helicobacter pylori in Gastric Epithelial Progenitors

• Published in: Proceedings of the National Academy of Sciences - PNAS 2005-04, Vol.102 (14), p.5186-5191
• Main Authors: Oh, Jung D., Karam, Sherif M., Gordon, Jeffrey I., Falkow, Stanley
• Format: Article
• Language: English
• Subjects: Animals; Bacteria; Biological Sciences; Cell lines; Cells; Epithelial cells; Epithelial Cells - cytology; Epithelial Cells - microbiology; Epithelium; Gastric Mucosa - cytology; Gastric Mucosa - microbiology; Gastritis, Atrophic - microbiology; Gastritis, Atrophic - pathology; Germ free animals; Germ-Free Life; Gnotobiotics; Helicobacter Infections - microbiology; Helicobacter Infections - pathology; Helicobacter pylori; Helicobacter pylori - isolation & purification; Helicobacter pylori - pathogenicity; Humans; Infections; Mice; Mice, Transgenic; Microscopy, Confocal; Microscopy, Electron; Multipotent Stem Cells - cytology; Multipotent Stem Cells - microbiology; Pathogens; Polysaccharides; Progenitor cells; Rodents; Stomach
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.0407657102

Helicobacter pylori is generally viewed as an extracellular pathogen. We have analyzed the tropism of H. pylori clinical isolates in a gnotobiotic transgenic mouse model of human chronic atrophic gastritis, a preneoplastic condition. These mice lack acid-producing parietal cells and have an amplified population of dividing gastric epithelial progenitors (GEPs) that express NeuAcα2,3Galβ1,4-glycans recognized by H. pylori adhesins. Scanning confocal and transmission electron microscopic studies of stomachs that had been colonized for 1 month or 1 year revealed intracellular bacterial collections (IBCs) in a small subset of multi- and oligopotential epithelial progenitors. Transmission electron microscopic and multilabel immunohistochemical analyses disclosed bacteria with several morphotypes, including spiral-shaped, in the cytoplasm and endosomes. Several stages in IBC evolution were documented, from a few solitary bacteria to consolidated populations in dividing and nondividing GEPs, to microorganisms traversing breaches in the GEP plasma cell membrane. IBC formation was not a unique feature of H. pylori strains isolated from patients with chronic atrophic gastritis. The notion that adult mammalian epithelial progenitors can function as a repository for H. pylori broadens the view of host habitats available to this and perhaps other pathogens.