title: Current concepts and controversies in prion immunopathology.
abstract: Scrapie in sheep and new variant Creutzfeldt-Jakob disease in humans are typically initiated by extracerebral exposure to prions. Both exhibit early prion accumulation in sites of the peripheral lymphoreticular system, such as splenic or lymph nodal germinal centers. In germinal centers, follicular dendritic cells (FDCs), whose development and maintenance depend on lymphotoxin and tumor necrosis factor signaling, are believed to be the main cell type for efficient prion replication in the periphery. Here, we discuss the molecular requirements for prion replication competence in stromal and lymphoid compartments of lymphoid organs. In addition, we examine the preconditions of transepithelial passage of prions in the mucosal-associated lymphoid system. Our results suggest that under specific conditions, efficient prion replication in mesenteric and inguinal lymph nodes is possible in the absence of mature FDCs. M cells are a plausible candidate for the mucosal portal of prion infection.
authors.affiliation: Institute of Neuropathology, University Hospital of Zürich CH-8091 Zürich, Switzerland.
authors.forename: Mathias
authors.initials: M
authors.lastname: Heikenwalder
authors.forename: Marco
authors.initials: M
authors.lastname: Prinz
authors.forename: Frank L
authors.initials: FL
authors.lastname: Heppner
authors.forename: Adriano
authors.initials: A
authors.lastname: Aguzzi
mesh_terms: D000818:Animals; D020566:Dendritic Cells, Follicular / Q000276:immunology / Q000378:metabolism; D004847:Epithelial Cells / Q000276:immunology / Q000378:metabolism; D006801:Humans; D007413:Intestinal Mucosa / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D008198:Lymph Nodes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D008233:Lymphotoxin-alpha / Q000276:immunology; D017096:Prion Diseases / Q000276:immunology* / Q000378:metabolism / Q000503:physiopathology; D011328:Prions / Q000276:immunology* / Q000378:metabolism / Q000472:pathogenicity*; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology
chemical_list: D008233:Lymphotoxin-alpha; D011328:Prions; D014409:Tumor Necrosis Factor-alpha