Projects per year
Abstract
After oral exposure, prions are thought to enter Peyer's patches via M cells and accumulate first upon follicular dendritic cells (FDCs) before spreading to the nervous system. How prions are actually initially acquired from the gut lumen is not known. Using high-resolution immunofluorescence and cryo-immunogold electron microscopy, we report the trafficking of the prion protein (PrP) toward Peyer's patches of wild-type and PrP-deficient mice. PrP was transiently detectable at 1 day post feeding (dpf) within large multivesicular LAMP1-positive endosomes of enterocytes in the follicle-associated epithelium (FAE) and at much lower levels within M cells. Subsequently, PrP was detected on vesicles in the late endosomal compartments of macrophages in the subepithelial dome. At 7-21 dpf, increased PrP labelling was observed on the plasma membranes of FDCs in germinal centres of Peyer's patches from wild-type mice only, identifying FDCs as the first sites of PrP conversion and replication. Detection of PrP on extracellular vesicles displaying FAE enterocyte-derived A33 protein implied transport towards FDCs in association with FAE-derived vesicles. By 21 dpf, PrP was observed on the plasma membranes of neurons within neighbouring myenteric plexi. Together, these data identify a novel potential M cell-independent mechanism for prion transport, mediated by FAE enterocytes, which acts to initiate conversion and replication upon FDCs and subsequent infection of enteric nerves.
Original language | English |
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Article number | e1002449 |
Journal | PLoS Pathogens |
Volume | 7 |
Issue number | 12 |
DOIs | |
Publication status | Published - 2011 |
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Dive into the research topics of 'Prion uptake in the gut: identification of the first uptake and replication sites'. Together they form a unique fingerprint.Projects
- 5 Finished
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ISPG programme 3 neurodegenerative diseases 2010-2011
Manson, J. (Principal Investigator)
1/08/10 → 31/07/11
Project: Research
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Priority - Protecting the food chain from prions shaping european priorities through basic and applied research
Mabbott, N. (Principal Investigator)
1/10/09 → 30/09/14
Project: Research
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