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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.
Mucosal Immunology
|February 2, 2012
Summary
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.
