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Processing and degradation of exogenous prion protein by CD11c(+) myeloid dendritic cells in vitro
Katarina M Luhr1, Robert P A Wallin, Hans-Gustaf Ljunggren
1Department of Neuroscience, Karolinska Institutet, SE-171 77 Stockholm, Sweden.
Abstract:
The immune system plays an important role in facilitating the spread of prion infections from the periphery to the central nervous system. CD11c(+) myeloid dendritic cells (DC) could, due to their subepithelial location and their migratory capacity, be early targets for prion infection and contribute to the spread of infection. In order to analyze mechanisms by which these cells may affect prion propagation, we studied in vitro the effect of exposing such DC to scrapie-infected GT1-1 cells, which produce the scrapie prion protein PrP(Sc). In this system, the DC efficiently engulfed the infected GT1-1 cells. Unexpectedly, PrP(Sc), which is generally resistant to protease digestion, was processed and rapidly degraded. Based on this observation we speculate that CD11c(+) DC may play a dual role in prion infections: on one hand they may facilitate neuroinvasion by transfer of the infectious agent as suggested from in vivo studies, but on the other hand they may protect against the infection by causing an efficient degradation of PrP(Sc). Thus, the migrating and highly proteolytic CD11c(+) myeloid DC may affect the balance between propagation and clearance of PrP(Sc) in the organism.
Insights
CD11c(+) myeloid dendritic cells (DCs) may combat prion infections by degrading the infectious prion protein PrP(Sc). However, these immune cells might also spread prion disease, suggesting a dual role in neuroinvasion and clearance.
Area of Science:
- Immunology
- Neuroscience
- Prion Biology
Background:
- The immune system is crucial for prion spread from the periphery to the central nervous system.
- CD11c(+) myeloid dendritic cells (DCs) are potential early targets for prion infection due to their location and migratory abilities.
Purpose of the Study:
- To investigate the mechanisms by which CD11c(+) DCs influence prion propagation.
- To analyze the interaction between dendritic cells and scrapie-infected cells producing PrP(Sc).
Main Methods:
- In vitro study exposing CD11c(+) DCs to scrapie-infected GT1-1 cells.
- Analysis of prion protein (PrP(Sc)) processing and degradation by DCs.
Main Results:
- CD11c(+) DCs efficiently engulfed infected GT1-1 cells.
- Unexpectedly, PrP(Sc), typically protease-resistant, was rapidly processed and degraded by DCs.
- This suggests a potential protective role for DCs in prion infections.
Conclusions:
- CD11c(+) myeloid DCs may have a dual role in prion infections: facilitating neuroinvasion and potentially protecting against infection through PrP(Sc) degradation.
- Migratory and proteolytic DCs could influence the balance between prion propagation and clearance in the body.