title: Orally administered prion protein is incorporated by m cells and spreads into lymphoid tissues with macrophages in prion protein knockout mice.
abstract: Transmissible spongiform encephalopathies are fatal neurodegenerative diseases. Infection by the oral route is assumed to be important, although its pathogenesis is not understood. Using prion protein (PrP) knockout mice, we investigated the sequence of events during the invasion of orally administered PrPs through the intestinal mucosa and the spread into lymphoid tissues and the peripheral nervous system. Orally administered PrPs were incorporated by intestinal epitheliocytes in the follicle-associated epithelium and villi within 1 hour. PrP-positive cells accumulated in the subfollicle region of Peyer's patches a few hours thereafter. PrP-positive cells spread toward the mesenteric lymph nodes and spleen after the accumulation of PrPs in the Peyer's patches. The number of PrP molecules in the mesenteric lymph nodes and spleen peaked at 2 days and 6 days after inoculation, respectively. The epitheliocytes in the follicle-associated epithelium incorporating PrPs were annexin V-positive microfold cells and PrP-positive cells in Peyer's patches and spleen were CD11b-positive and CD14-positive macrophages. Additionally, PrP-positive cells in Peyer's patches and spleen were detected in the vicinity of peripheral nerve fibers in the early stages of infection. These results indicate that orally delivered PrPs were incorporated by microfold cells promptly after challenge and that macrophages might act as a transporter of incorporated PrPs from the Peyer's patches to other lymphoid tissues and the peripheral nervous system.
authors.affiliation: Cellular Biology Laboratory, Graduate School of Agricultural Science, Tohoku University, Sendai, Japan.
authors.forename: Ikuro
authors.initials: I
authors.lastname: Takakura
authors.forename: Kohtaro
authors.initials: K
authors.lastname: Miyazawa
authors.forename: Takashi
authors.initials: T
authors.lastname: Kanaya
authors.forename: Wataru
authors.initials: W
authors.lastname: Itani
authors.forename: Kouichi
authors.initials: K
authors.lastname: Watanabe
authors.forename: Shyuichi
authors.initials: S
authors.lastname: Ohwada
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Watanabe
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Hondo
authors.forename: Michael T
authors.initials: MT
authors.lastname: Rose
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Mori
authors.forename: Suehiro
authors.initials: S
authors.lastname: Sakaguchi
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Nishida
authors.forename: Shigeru
authors.initials: S
authors.lastname: Katamine
authors.forename: Takahiro
authors.initials: T
authors.lastname: Yamaguchi
authors.forename: Hisashi
authors.initials: H
authors.lastname: Aso
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001921:Brain / Q000378:metabolism*; D007150:Immunohistochemistry; D007413:Intestinal Mucosa / Q000378:metabolism*; D007421:Intestine, Small / Q000378:metabolism; D008198:Lymph Nodes / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism*; D008297:Male; D008643:Mesentery / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D010581:Peyer's Patches / Q000378:metabolism* / Q000473:pathology; D017096:Prion Diseases / Q000209:etiology; D011328:Prions / Q000008:administration & dosage / Q000493:pharmacokinetics*; D013154:Spleen / Q000378:metabolism
chemical_list: D011328:Prions