M cell-depletion blocks oral prion disease pathogenesis

D. S. Donaldson, A. Kobayashi, H. Ohno, H. Yagita, I. R. Williams, N. A. Mabbott

Research output: Contribution to journalArticlepeer-review

60 Citations (Scopus)

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. 2012 Society for Mucosal Immunology.

Original languageEnglish
Pages (from-to)216-225
Number of pages10
JournalMucosal Immunology
Volume5
Issue number2
DOIs
Publication statusPublished - 2012 Mar

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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