Distribution of prion protein in the ileal Peyer’s patch of scrapie-free lambs and lambs naturally and experimentally exposed to the scrapie agent

Abstract

A sensitive immunohistochemical procedure was used to investigate the presence of prion protein (PrP) in the ileal Peyer's patch of PrP-genotyped lambs, including scrapie-free lambs and lambs naturally and experimentally exposed to the scrapie agent. The tyramide signal amplification system was used to enhance the sensitivity of conventional immunohistochemical procedures to show that PrP was widely distributed in the enteric nervous plexus supplying the gut wall. In scrapie-free lambs, PrP was also detected in scattered cells in the lamina propria and in the dome and interfollicular areas of the Peyer's patch. In the follicles, staining for PrP was mainly confined to the capsule and cells associated with vascular structures in the light central zone. In lambs naturally exposed to the scrapie agent, staining was prominent in the dome and neck region of the follicles and was also found to be associated with the follicle-associated epithelium. Similar observations were made in lambs that had received a single oral dose of scrapie-infected brain material from sheep with a homologous and heterologous PrP genotype 1 and 5 weeks previously. These studies show that the ileal Peyer's patch in young sheep may be an important site of uptake of the scrapie agent and that the biology of this major gut-associated lymphoid tissue may influence the susceptibility to oral infection in sheep. Furthermore, these studies suggest that homology or heterology between PrP genotypes or the presence of PrP genotypes seldom associated with disease does not impede uptake of PrP.

Pregnancy status and fetal prion genetics determine PrP Sc accumulation in placentomes of scrapie-infected sheep

“…In sheep, PrP Sc or scrapie infectivity is present primarily in tissues of the central and peripheral nervous system, lymphoreticular system, and placenta (9,(14)(15)(16)(17)(18)(19)(20)(21). Recent studies of reproductive and placental tissues from scrapie-infected pregnant sheep demonstrated that PrP Sc accumulates at the fetalmaternal interface (the placentome) and proposed that scrapie is not transmitted in utero, but may be transmitted from infected dams to their scrapie susceptible lambs during the perinatal period by exposure to infectious placental tissues (9).…”

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

“…Macrophages containing PrP Sc have been detected in ovine Peyer's patches, 46 other secondary lymph nodes of variant CJD patients, 47 and the spleen of mice. 48 In the spleen, PrP-positive cells were entirely CD14-positive macrophages (Figure 8).…”

The use of non-prion biomarkers for the diagnosis of Transmissible Spongiform Encephalopathies in the live animal

“…In contrast, sheep deliberately challenged with BSE display PrP Sc in a broad range of tissues including the lymphoid system, parts of the digestive tract and in the peripheral nervous system [29]. The distribution of infectivity in these BSE affected sheep is similar to that observed in sheep of similar PrP-genotype infected with scrapie [9, 42,62,63]. The spread of PrP Sc to the lymphoid organs is thought to be mediated by the lymphoreticular system.…”