Increased Abundance of M
Cells in the Gut Epithelium Dramatically Enhances Oral Prion Disease
Susceptibility
Affiliation The Roslin
Institute & Royal (Dick) School of Veterinary Sciences, University of
Edinburgh, United Kingdom
- Anuj Sehgal,
Affiliation The Roslin
Institute & Royal (Dick) School of Veterinary Sciences, University of
Edinburgh, United Kingdom
- Daniel Rios,
Current address: The Broad
Institute of MIT and Harvard, Cambridge, Massachusetts, United States of
America
Affiliation Dept.
Pathology, Emory University School of Medicine, Atlanta, Georgia, United States
of America
- Ifor R. Williams,
Affiliation Dept.
Pathology, Emory University School of Medicine, Atlanta, Georgia, United States
of America
- Neil A. Mabbott
* E-mail:
neil.mabbott@roslin.ed.ac.uk
Affiliation The Roslin
Institute & Royal (Dick) School of Veterinary Sciences, University of
Edinburgh, United Kingdom
⨯
Increased Abundance of M Cells in the Gut Epithelium Dramatically Enhances Oral Prion Disease Susceptibility
- David S. Donaldson,
- Anuj Sehgal,
- Daniel Rios,
- Ifor R. Williams,
- Neil A. Mabbott
x
- Published: December 14, 2016
- http://dx.doi.org/10.1371/journal.ppat.1006075
Abstract
Author Summary
snip...
In conclusion, we show
that the initial uptake and transfer of prions across the gut epithelium in association
with M cells is essential to establish host infection. Importantly, we also
demonstrate that the density of M cells in the FAE overlying the Peyer’s
patches in the small intestine directly controls the efficiency of oral prion
infection. In the specific absence of M cells, the uptake and accumulation of
prions in Peyer’s patches and their subsequent spread to the MLN and spleen is
blocked. In contrast, oral prion disease susceptibility was enhanced
approximately 10-fold in mice in which M cell-deficiency in the gut epithelium
was increased. Thus, M cells could be considered as the gatekeepers of oral
prion infection whose density directly limits or enhances disease
susceptibility. Further studies are necessary to determine whether most orally
acquired prion strains similarly exploit intestinal M cells to establish host
infection after oral exposure, but data from independent in vivo and in vitro studies using
mouse-passaged RML scrapie prions [30],
Fukuoka-1 prions [31],
BSE prions [32]
and 263K hamster prions [17]
imply a similar requirement. Antigen sampling M cells are also present in the
FAE overlying the NALT in the nasal cavity [44,
45],
but data from the analysis of prion disease pathogenesis in hamsters implies
that the requirement for M cell-mediated uptake may vary depending on the route
of exposure [85].
After intra-nasal exposure some transient uptake of 263K prions was observed in
M cells within the FAE overlying the NALT, but a greater magnitude of
paracellular transport across the epithelia within the nasal cavity was also
noted [85].
Although certain concurrent pathogen infections, inflammatory stimuli and aging
may have multiple effects on the gut epithelium, our data suggest that factors
such as these that can modify M cell-density in the small intestine [25,
39,
40,
71]
may represent important risk factors which can significantly influence
susceptibility to orally-acquired prion infections. Our data also raise the
possibility that the density of M cells in the gut epithelium may similarly
influence susceptibility to other important orally-acquired bacterial and viral
pathogens which are considered to exploit M cells to infect the host [24–28].
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