title: Infected splenic dendritic cells are sufficient for prion transmission to the CNS in mouse scrapie.
abstract: Transmissible spongiform encephalopathies display long incubation periods at the beginning of which the titer of infectious agents (prions) increases in peripheral lymphoid organs. This "replication" leads to a progressive invasion of the CNS. Follicular dendritic cells appear to support prion replication in lymphoid follicles. However, the subsequent steps of neuroinvasion remain obscure. CD11c(+) dendritic cells, an unrelated cell type, are candidate vectors for prion propagation. We found a high infectivity titer in splenic dendritic cells from prion-infected mice, suggesting that dendritic cells carry infection. To test this hypothesis, we injected RAG-1(0/0) mice intravenously with live spleen cell subsets from scrapie-infected donors. Injection of infected dendritic cells induced scrapie without accumulation of prions in the spleen. These results suggest that CD11c(+) dendritic cells can propagate prions from the periphery to the CNS in the absence of any additional lymphoid element.
authors.affiliation: Institut National de la Santé et de la Recherche Médicale (INSERM) U25 and Centre National de la Recherche Scientifique U8603, Hôpital Necker, Paris, France. aucouturier@necker.fr
authors.forename: P
authors.initials: P
authors.lastname: Aucouturier
authors.forename: F
authors.initials: F
authors.lastname: Geissmann
authors.forename: D
authors.initials: D
authors.lastname: Damotte
authors.forename: G P
authors.initials: GP
authors.lastname: Saborio
authors.forename: H C
authors.initials: HC
authors.lastname: Meeker
authors.forename: R
authors.initials: R
authors.lastname: Kascsak
authors.forename: R
authors.initials: R
authors.lastname: Kascsak
authors.forename: R I
authors.initials: RI
authors.lastname: Carp
authors.forename: T
authors.initials: T
authors.lastname: Wisniewski
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D003713:Dendritic Cells / Q000737:chemistry / Q000502:physiology* / Q000637:transplantation; D016654:Genes, RAG-1; D016167:Integrin alphaXbeta2 / Q000032:analysis; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018620:PrPSc Proteins / Q000032:analysis; D011328:Prions / Q000472:pathogenicity*; D012608:Scrapie / Q000276:immunology / Q000473:pathology / Q000635:transmission*; D013154:Spleen / Q000033:anatomy & histology / Q000473:pathology*
chemical_list: D016167:Integrin alphaXbeta2; D018620:PrPSc Proteins; D011328:Prions