TY - JOUR
T1 - Prion uptake in the gut
T2 - identification of the first uptake and replication sites
AU - Kujala, P.
AU - Raymond, C.R.
AU - Romeijn, M.
AU - Godsave, S.F.
AU - van Kasteren, S.I.
AU - Wille, H.
AU - Prusiner, S.B.
AU - Mabbott, N.A.
AU - Peters, P.J.
N1 - 22216002
Kujala, Pekka Raymond, Claudine R Romeijn, Martijn Godsave, Susan F van Kasteren, Sander I Wille, Holger Prusiner, Stanley B Mabbott, Neil A Peters, Peter J United States PLoS pathogens PLoS Pathog. 2011 Dec;7(12):e1002449. Epub 2011 Dec 22.
PY - 2011
Y1 - 2011
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84855290942&partnerID=8YFLogxK
U2 - 10.1371/journal.ppat.1002449
DO - 10.1371/journal.ppat.1002449
M3 - Article
SN - 1553-7366
VL - 7
JO - PLoS Pathogens
JF - PLoS Pathogens
IS - 12
M1 - e1002449
ER -