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M cell-depletion blocks oral prion disease pathogenesis
D S Donaldson1, A Kobayashi, H Ohno
1The Roslin Institute and Royal (Dick) School of Veterinary Sciences, University of Edinburgh, Edinburgh, UK.
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.
Insights
Microfold (M) cells in the gut are crucial for prion diseases acquired orally. Blocking M cells prevents prion accumulation and spread to the brain, highlighting their role in disease transmission.
Area of Science:
- Neuroscience
- Immunology
- Microbiology
Background:
- Prion diseases can be acquired through oral ingestion.
- Efficient neuroinvasion requires early prion replication in Peyer's patches.
- The mechanism of prion transport across the gut epithelium into Peyer's patches is not fully understood.
Purpose of the Study:
- To investigate the role of microfold (M) cells in the oral uptake of prions.
- To determine if M cells are essential for prion transport into Peyer's patches and subsequent neuroinvasion.
Main Methods:
- Depletion of M cells in the gut-associated lymphoid tissue.
- Oral exposure to prions.
- Assessment of prion accumulation on follicular dendritic cells (FDC) in Peyer's patches.
- Monitoring for neuroinvasion and disease development.
Main Results:
- Depletion of M cells significantly blocked early prion accumulation on FDC in Peyer's patches.
- Absence of M cells at the time of oral exposure prevented neuroinvasion and disease development.
- These findings indicate that M cells are critical for initial prion uptake from the gut.
Conclusions:
- Microfold (M) cells are essential for the efficient oral acquisition of prion diseases.
- M cells facilitate prion transport from the gut lumen into Peyer's patches, a key step for neuroinvasion.
- Targeting M cells could be a strategy to prevent prion disease transmission.
