M cell-depletion blocks oral prion disease pathogenesis

• Type of Material: Article
• 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
• Language: English
• Date: 2012-03-01
• Publisher: Nature Publishing Group
• Publication Version: Final Published Version
• Copyright Statement: © 2012 Society for Mucosal Immunology.
• License: Creative Commons Attribution-NonCommerical-NoDerivs 3.0 Unported
• Final Published Version (URL): http://dx.doi.org/10.1038/mi.2011.68
• Title of Journal or Parent Work: Mucosal Immunology
• ISSN: 1933-0219
• Volume: 5
• Issue: 2
• Start Page: 216
• End Page: 225
• Grant/Funding Information: This work was supported by Grant funding from the University of Edinburgh Development Fund and by project (BB/G003947-1) and Institute Strategic Programme Grant funding from the Biotechnology and Biological Sciences Research Council.; AK is supported by a Japan Society for the Promotion of Science Fellowship for Research Abroad and natural sciences Grant funding from the Mitsubishi Foundation.
• Keywords: PROTEIN; SCRAPIE AGENT NEUROINVASION; IN-VIVO; LYMPHOID-TISSUES; Immunology; TUMOR-NECROSIS-FACTOR; Life Sciences & Biomedicine; Science & Technology; DENDRITIC CELLS; FOLLICLE-ASSOCIATED EPITHELIUM; PEYERS PATCH; PATCH M-CELLS; INFECTION
• Research Categories: Health Sciences, Pathology; Health Sciences, Immunology

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.