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Updated: Jul 14, 2026
Monitoring Immune Cells Trafficking Fluorescent Prion Rods Hours after Intraperitoneal Infection
Published on: November 19, 2010
Infected splenic dendritic cells are sufficient for prion transmission to the CNS in mouse scrapie
P Aucouturier1, F Geissmann, D Damotte
1Institut 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
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.
Insights
Dendritic cells, a type of immune cell, may spread prions from the body to the brain. This study shows these cells can cause prion disease in mice without needing other immune cells.
Area of Science:
- Neuroscience
- Immunology
- Infectious Diseases
Background:
- Transmissible spongiform encephalopathies (TSEs) are fatal neurodegenerative diseases.
- Prions replicate in peripheral lymphoid organs before invading the central nervous system (CNS).
- The exact mechanism of prion neuroinvasion remains unclear, though follicular dendritic cells are implicated in lymphoid prion replication.
Purpose of the Study:
- To investigate the role of CD11c(+) dendritic cells in prion propagation and neuroinvasion.
- To determine if dendritic cells can transmit prion disease independently of other lymphoid elements.
Main Methods:
- Mice deficient in RAG-1 (RAG-1(0/0)) were used, lacking mature lymphocytes.
- Spleen cell subsets, including CD11c(+) dendritic cells, were isolated from scrapie-infected mice.
- These cell subsets were intravenously injected into RAG-1(0/0) recipient mice.
Main Results:
- A high prion infectivity titer was detected in splenic dendritic cells from infected mice.
- Intravenous injection of infected dendritic cells induced scrapie in recipient mice.
- Scrapie developed in recipient mice even without prion accumulation in the spleen, suggesting direct propagation.
Conclusions:
- CD11c(+) dendritic cells are efficient carriers of prion infection.
- Dendritic cells can propagate prions from the periphery to the CNS.
- This prion propagation occurs independently of other lymphoid components, highlighting their critical role in neuroinvasion.
