Infected splenic dendritic cells are sufficient for prion transmission to the CNS in mouse scrapie

Transmissible spongiform encephalopathies display long incubation periods a t the beginning of which the titer of infectious agents (prions) increases in peripheral lymphoid organs. This "replication" leads to a progressive in vasion of the CNS. Follicular dendritic cells appear to support prion repli cation in lymphoid follicles. However, the subsequent steps of neuroinvasio n remain obscure. CD11c(+) dendritic cells, an unrelated cell type, are can didate 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) mic e 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 cel ls can propagate prions from the periphery to the CNS in the absence of any additional lymphoid element.