Infected splenic dendritic cells are sufficient for prion transmission to the CNS in mouse scrapie
P Aucouturier, F Geissmann, D Damotte, G P Saborio, H C Meeker, R Kascsak, R Kascsak, R I Carp, T Wisniewski, P Aucouturier, F Geissmann, D Damotte, G P Saborio, H C Meeker, R Kascsak, R Kascsak, R I Carp, T Wisniewski
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.
Figures
Source: PubMed