title: M cell-depletion blocks oral prion disease pathogenesis.
abstract: Many prion diseases are orally acquired. Our data show that after oral exposure, early prion replication upon follicular dendritic cells (FDC) in Peyer's patches is obligatory for the efficient spread of disease to the brain (termed neuroinvasion). For prions to replicate on FDC within Peyer's patches after ingestion of a contaminated meal, they must first cross the gut epithelium. However, the mechanism through which prions are conveyed into Peyer's patches is uncertain. Within the follicle-associated epithelium overlying Peyer's patches are microfold cells (M cells), unique epithelial cells specialized for the transcytosis of particles. We show that following M cell-depletion, early prion accumulation upon FDC in Peyer's patches is blocked. Furthermore, in the absence of M cells at the time of oral exposure, neuroinvasion and disease development are likewise blocked. These data suggest M cells are important sites of prion uptake from the gut lumen into Peyer's patches.
authors.affiliation: The Roslin Institute and Royal (Dick) School of Veterinary Sciences, University of Edinburgh, Edinburgh, UK.
authors.forename: D S
authors.initials: DS
authors.lastname: Donaldson
authors.forename: A
authors.initials: A
authors.lastname: Kobayashi
authors.forename: H
authors.initials: H
authors.lastname: Ohno
authors.forename: H
authors.initials: H
authors.lastname: Yagita
authors.forename: I R
authors.initials: IR
authors.lastname: Williams
authors.forename: N A
authors.initials: NA
authors.lastname: Mabbott
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001921:Brain / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D002454:Cell Differentiation / Q000235:genetics; D002478:Cells, Cultured; D020566:Dendritic Cells, Follicular / Q000276:immunology* / Q000473:pathology; D018450:Disease Progression; D004435:Eating; D020895:Enterocytes / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D004781:Environmental Exposure / Q000009:adverse effects; D008460:Meat; D051379:Mice; D018345:Mice, Knockout; D010581:Peyer's Patches / Q000276:immunology* / Q000473:pathology; D017096:Prion Diseases / Q000276:immunology* / Q000473:pathology / Q000517:prevention & control / Q000635:transmission; D011328:Prions / Q000276:immunology*; D053245:RANK Ligand / Q000276:immunology*; D057900:Transcytosis / Q000235:genetics / Q000276:immunology
chemical_list: D011328:Prions; D053245:RANK Ligand