title: Oral prion infection requires normal numbers of Peyer's patches but not of enteric lymphocytes.
abstract: Prion pathogenesis following oral exposure is thought to involve gut-associated lymphatic tissue, which includes Peyer's patches (PPs) and M cells. Recruitment of activated B lymphocytes to PPs requires alpha(4)beta(7) integrin; PPs of beta 7(-/-) mice are normal in number but are atrophic and almost entirely devoid of B cells. Here we report that minimal infectious dose and disease incubation after oral exposure to logarithmic dilutions of prion inoculum were similar in beta 7(-/-) and wild-type mice, and PPs of both beta 7(-/-) and wild-type mice contained 3-4 log LD(50)/g prion infectivity > or =125 days after challenge. Despite marked reduction of B cells, M cells were present in beta 7(-/-) mice. In contrast, mice deficient in both tumor necrosis factor and lymphotoxin-alpha (TNF alpha(-/-) x LT alpha(-/-)) or in lymphocytes (RAG-1(-/-), mu MT), in which numbers of PPs are reduced in number, were highly resistant to oral challenge, and their intestines were virtually devoid of prion infectivity at all times after challenge. Therefore, lymphoreticular requirements for enteric and for intraperitoneal uptake of prions differ from each other. Although susceptibility to prion infection following oral challenge correlates with the number of PPs, it is remarkably independent of the number of PP-associated lymphocytes.
authors.affiliation: Institute of Neuropathology, University Hospital of Zürich, Zürich, Switzerland.
authors.forename: Marco
authors.initials: M
authors.lastname: Prinz
authors.forename: Gerhard
authors.initials: G
authors.lastname: Huber
authors.forename: Andrew J S
authors.initials: AJ
authors.lastname: Macpherson
authors.forename: Frank L
authors.initials: FL
authors.lastname: Heppner
authors.forename: Markus
authors.initials: M
authors.lastname: Glatzel
authors.forename: Hans-Pietro
authors.initials: HP
authors.lastname: Eugster
authors.forename: Norbert
authors.initials: N
authors.lastname: Wagner
authors.forename: Adriano
authors.initials: A
authors.lastname: Aguzzi
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology / Q000473:pathology; D018398:Homeodomain Proteins / Q000235:genetics; D039641:Integrin beta Chains / Q000235:genetics; D008214:Lymphocytes / Q000473:pathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010581:Peyer's Patches / Q000473:pathology*; D012608:Scrapie / Q000276:immunology / Q000473:pathology*; D014409:Tumor Necrosis Factor-alpha / Q000172:deficiency / Q000235:genetics / Q000502:physiology
chemical_list: D018398:Homeodomain Proteins; D039641:Integrin beta Chains; D014409:Tumor Necrosis Factor-alpha; C091368:integrin beta7; C064658:RAG-1 protein