Infected splenic dendritic cells are sufficient for prion transmission to the CNS in mouse scrapie.
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.
Aucouturier
P
P
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
Geissmann
F
F
Damotte
D
D
Saborio
G P
GP
Meeker
H C
HC
Kascsak
R
R
Kascsak
R
R
Carp
R I
RI
Wisniewski
T
T
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*
D016167:Integrin alphaXbeta2; D018620:PrPSc Proteins; D011328:Prions