M cell-depletion blocks oral prion disease pathogenesis

• Authors: DS Donaldson, University of Edinburgh; A Kobayashi, University of Edinburgh; H Ohno, RIKEN; H Yagita, Juntendo University; Ifor Williams, Emory University; NA Mabbott, University of Edinburgh
• Journal Title: Mucosal Immunology
• Volume: Volume 5, Number 2
• Publisher: Nature Publishing Group | 2012-03-01, Pages 216-225
• Type of Work: Article | Final Publisher PDF
• Publisher DOI: http://doi.org/10.1038/mi.2011.68
• Subjects: Health Sciences, Immunology; Health Sciences, Pathology
• Keywords: Science & Technology; Life Sciences & Biomedicine; Immunology; FOLLICLE-ASSOCIATED EPITHELIUM; SCRAPIE AGENT NEUROINVASION; TUMOR-NECROSIS-FACTOR; PATCH M-CELLS; PEYERS PATCH; DENDRITIC CELLS; LYMPHOID-TISSUES; IN-VIVO; PROTEIN; INFECTION

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.