期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 102, 期 14, 页码 5186-5191出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.0407657102
关键词
adult mammalian epithelial progenitors; bacterial pathogenesis; intracellular bacterial communities; gnotobiotic mice; chronic atrophic gastritis
资金
- NIDDK NIH HHS [DK63483, DK58529, U01 DK063483, R01 DK058529] Funding Source: Medline
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 NeuAc alpha 2,3Gal beta 1,4-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.
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