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Updated: Jun 7, 2026
Monitoring Immune Cells Trafficking Fluorescent Prion Rods Hours after Intraperitoneal Infection
Published on: November 19, 2010
Prion replication in the hematopoietic compartment is not required for neuroinvasion in scrapie mouse model
Corinne Loeuillet1, Catherine Lemaire-Vieille, Philippe Naquet
1Laboratoire Adaptation et Pathogénie des Micro-organismes, Centre National Recherche Scientifique UMR 5163, Université Joseph Fourier, Grenoble, France.
Abstract:
Fatal neurodegenerative prion diseases are caused by the transmissible PrP(Sc) prion agent whose initial replication after peripheral inoculation takes place in follicular dendritic cells present in germinal centers of lymphoid organs. However, prion replication also occurs in lymphoid cells. To assess the role of the hematopoietic compartment in neuroinvasion and prion replication, we generated chimeric mice, on a uniform congenic C57/BL6J background, by bone marrow replacement with hematopoietic cells expressing different levels of PrP protein. Nine different types of chimeric mice were inoculated intraperitoneally either with the lymphotropic Rocky Mountain Laboratory (RML) strain or the non lymphotropic ME-7 scrapie strain, at different doses. Here, we clearly demonstrate that overexpression of PrP by the hematopoietic system, or the lack of PrP expression by the bone marrow derived cells, does not change the incubation time period of the disease, even when the mice are infected at limiting doses. We conclude that the hematopoietic compartment is more or less permissive to prion replication, both for RML and ME-7, but does not play a role in neuroinvasion.
Insights
The hematopoietic system does not influence prion disease neuroinvasion. Bone marrow-derived cells
Area of Science:
- Neuroscience
- Immunology
- Infectious Diseases
Background:
- Fatal neurodegenerative prion diseases stem from transmissible prion agents (PrPSc).
- Initial prion replication occurs in lymphoid organs' germinal centers, specifically follicular dendritic cells.
- Prion replication is also observed in lymphoid cells, suggesting a role for the hematopoietic system.
Purpose of the Study:
- To investigate the role of the hematopoietic compartment in prion disease neuroinvasion and replication.
- To determine if varying levels of PrP expression in hematopoietic cells affect disease progression.
Main Methods:
- Generation of chimeric mice with different PrP expression levels in hematopoietic cells.
- Intraperitoneal inoculation of chimeric mice with Rocky Mountain Laboratory (RML) or ME-7 prion strains.
- Assessment of incubation periods and disease progression following prion infection.
Main Results:
- Overexpression or lack of PrP in hematopoietic cells did not alter disease incubation times.
- Hematopoietic compartment permissiveness to prion replication varied but did not impact neuroinvasion.
- No significant difference in incubation periods was observed even with limiting prion doses.
Conclusions:
- The hematopoietic compartment is permissive but not essential for prion replication.
- Hematopoietic cells do not play a critical role in the neuroinvasion process of prion diseases.
- Prion disease pathogenesis is independent of PrP expression levels in bone marrow-derived cells.
