Early accumulation of pathological PrP in the enteric nervous system and gut-associated lymphoid tissue of hamsters orally infected with scrapie

Follicular Dendritic Cell Dedifferentiation by Treatment with an Inhibitor of the Lymphotoxin Pathway Dramatically Reduces Scrapie Susceptibility

“…Second, since the effects of LT␤R-Ig on FDC status are temporary (22,40), do consecutive doses of LT␤R-Ig prolong the period of FDC dedifferentiation and, if so, does this further reduce disease susceptibility? Finally, since early PrP Sc accumulation occurs upon FDCs after oral inoculation of rodents (3) and sheep (1,23) with scrapie and of mule deer with CWD (54), are FDCs important for TSE pathogenesis after oral inoculation? To address this question, mice were treated with LT␤R-Ig before or shortly after oral scrapie inoculation to determine whether temporary FDC dedifferentiation reduced susceptibility to orally inoculated scrapie and, if so, how long after inoculation such intervention was possible?…”

“…Peyer's patches are the primary inductive sites in gut-associated lymphoid tissues that actively acquire antigens from the lumen of the intestine. After intragastric or oral inoculation of rodents with scrapie, infectivity and PrP Sc accumulate first in Peyer's patches, gut-associated lymphoid tissues, and ganglia of the enteric nervous system long before their detection in the CNS (3,30,41,45). Natural sheep scrapie may also be acquired orally as PrP Sc is detected in Peyer's patches and gut-associated lymphoid tissues (1) prior to detection within the CNS (57).…”

“…The lack of any observable effect of LT␤R-Ig treatment on disease pathogenesis when given 14 days after oral inoculation is therefore consistent with the hypothesis that neuroinvasion has already occurred. Recent studies have demonstrated that PrP Sc accumulates within enteric ganglia soon after oral inoculation (3,45). In the Peyer's patch, FDC networks are situated distal from the gut lumen and lie in close association with nerve fibres that run along the gut wall (3).…”

Orally Administered Prion Protein Is Incorporated by M Cells and Spreads into Lymphoid Tissues with Macrophages in Prion Protein Knockout Mice

“…We first observed the uptake and internalization of orally delivered PrPs by annexin V-positive M cells within the FAE. Several in vivo 33 and in vitro 9,34 studies suggest that M cells act as the portal sites for orally administered infectious agents. Additionally, we observed that villous epithelial cells also incorporated PrPs.…”

Les prions exploitent les communications neuro-immunitaires

“…Des cellules ganglionnaires trabé culaires germinatifs, qui caractérise les plaques de Peyer par rapport à la rate, serait responsable d'une neuro-invasion plus rapide à partir des plaques de Peyer [16]. Un second mécanisme ferait intervenir des cellules immunitaires présentes au sein des centres germinatifs, qui serviraient de pont cellulaire actif lors de la neuro-invasion.…”