title: Human tonsil-derived follicular dendritic-like cells are refractory to human prion infection in vitro and traffic disease-associated prion protein to lysosomes.
abstract: The molecular mechanisms involved in human cellular susceptibility to prion infection remain poorly defined. This is due, in part, to the absence of any well characterized and relevant cultured human cells susceptible to infection with human prions, such as those involved in Creutzfeldt-Jakob disease. In variant Creutzfeldt-Jakob disease, prion replication is thought to occur first in the lymphoreticular system and then spread into the brain. We have, therefore, examined the susceptibility of a human tonsil-derived follicular dendritic cell-like cell line (HK) to prion infection. HK cells were found to display a readily detectable, time-dependent increase in cell-associated abnormal prion protein (PrP(TSE)) when exposed to medium spiked with Creutzfeldt-Jakob disease brain homogenate, resulting in a coarse granular perinuclear PrP(TSE) staining pattern. Despite their high level of cellular prion protein expression, HK cells failed to support infection, as judged by longer term maintenance of PrP(TSE) accumulation. Colocalization studies revealed that exposure of HK cells to brain homogenate resulted in increased numbers of detectable lysosomes and that these structures immunostained intensely for PrP(TSE) after exposure to Creutzfeldt-Jakob disease brain homogenate. Our data suggest that human follicular dendritic-like cells and perhaps other human cell types are able to avoid prion infection by efficient lysosomal degradation of PrP(TSE).
authors.affiliation: National Creutzfeldt-Jakob Disease Research & Surveillance Unit, Centre for Clinical Brain Sciences, University of Edinburgh, Edinburgh, United Kingdom.
authors.forename: Zuzana
authors.initials: Z
authors.lastname: Krejciova
authors.affiliation: Centre for Regenerative Medicine, University of Edinburgh, Edinburgh, United Kingdom.
authors.forename: Paul
authors.initials: P
authors.lastname: De Sousa
authors.affiliation: Neurobiology Division, The Roslin Institute and Royal (Dick) School of Veterinary Studies, University of Edinburgh, Easter Bush, United Kingdom.
authors.forename: Jean
authors.initials: J
authors.lastname: Manson
authors.affiliation: National Creutzfeldt-Jakob Disease Research & Surveillance Unit, Centre for Clinical Brain Sciences, University of Edinburgh, Edinburgh, United Kingdom.
authors.forename: James W
authors.initials: JW
authors.lastname: Ironside
authors.affiliation: National Creutzfeldt-Jakob Disease Research & Surveillance Unit, Centre for Clinical Brain Sciences, University of Edinburgh, Edinburgh, United Kingdom. Electronic address: m.w.head@ed.ac.uk.
authors.forename: Mark W
authors.initials: MW
authors.lastname: Head
mesh_terms: D002460:Cell Line; D007562:Creutzfeldt-Jakob Syndrome / Q000378:metabolism; D020566:Dendritic Cells, Follicular / Q000378:metabolism*; D005455:Fluorescent Antibody Technique; D006801:Humans; D008247:Lysosomes / Q000378:metabolism*; D018613:Microscopy, Confocal; D014066:Palatine Tonsil / Q000166:cytology; D018620:PrPSc Proteins / Q000378:metabolism*
chemical_list: D018620:PrPSc Proteins