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Infected splenic dendritic cells are sufficient for prion transmission to the CNS in mouse scrapie
Pierre Aucouturier, Frédéric Geissmann, Diane Damotte, Gabriela P. Saborio, Harry C. Meeker, Regina Kascsak, Richard Kascsak, Richard I. Carp, Thomas Wisniewski
Pierre Aucouturier, Frédéric Geissmann, Diane Damotte, Gabriela P. Saborio, Harry C. Meeker, Regina Kascsak, Richard Kascsak, Richard I. Carp, Thomas Wisniewski
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Article

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

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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-10/0 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

Pierre Aucouturier, Frédéric Geissmann, Diane Damotte, Gabriela P. Saborio, Harry C. Meeker, Regina Kascsak, Richard Kascsak, Richard I. Carp, Thomas Wisniewski

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Figure 2

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Absence of lymphoid reconstitution in mice injected with infected CD11c+...
Absence of lymphoid reconstitution in mice injected with infected CD11c+ cells. (a–d) Hematoxylin and eosin staining of paraformaldehyde-fixed sections at the same magnification. ×25. A normal lymphoid architecture of the spleen is found in RAG10/0 mice that had been injected with live total spleen cells (a) and the B cell–enriched fraction (b), but not in RAG10/0 mice injected with killed spleen cells (c) or the live CD11c+ cell–enriched fraction (d). (e and f) Higher magnification (×1,000) of lymphoid follicles in spleens from mice injected with total spleen cells (e) reveals typical aspect including immunoblasts and centroblast, which is clearly different from that of nodules found in spleens from CD11C+ cell–injected mice (f); the latter are made of smaller cells, essentially with a nonlymphoid morphology and likely belonging to other hematopoietic lineages. (g and h) Frozen sections from spleens of RAG10/0 mouse recipients injected with total spleen cells (g; ×400) or the CD11c+ cell–enriched fraction (h; ×400) were triple stained with anti-CD3-FITC (green), anti-CD19-phycoerythrin (red), and anti-CD11c-Cychrome5 (blue). The absence of lymphoid structure in RAG10/0 mice injected with CD11c+ cells is confirmed on h, which is representative of the entire spleen and shows no staining for B (CD19) and T (CD3) cells. (i and j) Immunohistochemical evidence of PrPSc (see Methods) accumulation in spleens from RAG10/0 mice infected with total spleen cells (i; ×200) but not in those from mice infected with the CD11c+ cell–enriched fraction (j; ×200).

Copyright © 2025 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)

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