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Journal of Virology, December 2002, p. 12259-12264, Vol. 76, No. 23
0022-538X/02/$04.00+0 DOI: 10.1128/JVI.76.23.12259-12264.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.
Processing and Degradation of Exogenous Prion Protein by CD11c+ Myeloid Dendritic Cells In Vitro
Katarina M. Luhr,1 Robert P. A. Wallin,2 Hans-Gustaf Ljunggren,2 Peter Löw,1 Albert Taraboulos,3 and Krister Kristensson1*
Department of Neuroscience,1
Microbiology and Tumor Biology Center, Karolinska Institutet, SE-171 77 Stockholm, Sweden,2
Department of Molecular Biology, Hebrew University Hadassah Medical School, 91120 Jerusalem, Israel3
Received 28 March 2002/
Accepted 19 August 2002
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 PrPSc. In this system, the DC efficiently engulfed the infected GT1-1 cells. Unexpectedly, PrPSc, 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 PrPSc. Thus, the migrating and highly proteolytic CD11c+ myeloid DC may affect the balance between propagation and clearance of PrPSc in the organism.
* Corresponding author. Mailing address: Department of Neuroscience, Karolinska Institutet, Retzius väg 8, Stockholm SE-171 77, Sweden. Phone: 46-8-728 78 25. Fax: 46-8-32 53 25. E-mail:
Krister.Kristensson{at}neuro.ki.se.
Journal of Virology, December 2002, p. 12259-12264, Vol. 76, No. 23
0022-538X/02/$04.00+0 DOI: 10.1128/JVI.76.23.12259-12264.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.
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