Intracellular Helicobacter pylori in gastric epithelial progenitors.
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.
Oh
Jung D
JD
Center for Genome Sciences and Department of Molecular Biology and Pharmacology, Washington University School of Medicine, St. Louis, MO 63108, USA.
Karam
Sherif M
SM
Gordon
Jeffrey I
JI
D000818:Animals; D004847:Epithelial Cells / Q000166:cytology / Q000382:microbiology; D005753:Gastric Mucosa / Q000166:cytology / Q000382:microbiology*; D005757:Gastritis, Atrophic / Q000382:microbiology / Q000473:pathology; D005856:Germ-Free Life; D016481:Helicobacter Infections / Q000382:microbiology / Q000473:pathology; D016480:Helicobacter pylori / Q000302:isolation & purification* / Q000472:pathogenicity*; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D018613:Microscopy, Confocal; D008854:Microscopy, Electron; D039902:Multipotent Stem Cells / Q000166:cytology / Q000382:microbiology