Early accumulation of PrPSc in gut-associated lymphoid and nervous tissuesof susceptible sheep from a Romanov flock with natural scrapie

The immune system is known to be involved in the early phase of scrapie pat hogenesis. However, the infection route of naturally occurring scrapie and its spread within the host are not entirely known. In this study, the patho genesis of scrapie was investigated in sheep of three PrP genotypes, from 2 to 9 months of age, which were born and raised together in a naturally scr apie-affected Romanov Rock. The kinetics of PrPSc accumulation in sheep org ans were determined by immunohistochemistry. PrPSc was detected only in sus ceptible VRQ/VRQ sheep, from 2 months of age, with an apparent entry site a t the ileal Peyer's patch as well as its draining mesenteric lymph node. At the cellular level, PrPSc deposits were associated with CD68-positive cell s of the dome area and B follicles before being detected in follicular dend ritic cells. In 3- to 6-month-old sheep, PrPSc was detected in most of the gut-associated lymphoid tissues (GALT) and to a lesser extent in more syste mic lymphoid formations such as the spleen or the mediastinal lymph node. A ll secondary lymphoid organs showed a similar intensity of PrPSc-immunolabe lling at 9 months of age. At this time-point, PrPSc was also detected in th e autonomic myenteric nervous plexus and in the nucleus parasympathicus ner vi X of the brain stem. These data suggest that natural scrapie infection o ccurs by the oral route via infection of the Peyer's patches followed by re plication in the GALT. It may then spread to the central nervous system thr ough the autonomic nervous fibres innervating the digestive tract.