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Journal of Virology, May 2006, p. 4656-4663, Vol. 80, No. 10
0022-538X/06/$08.00+0     doi:10.1128/JVI.80.10.4656-4663.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Processing of the Bovine Spongiform Encephalopathy-Specific Prion Protein by Dendritic Cells

Catherine Rybner-Barnier,1,2 Catherine Jacquemot,1,2 Céline Cuche,2 Grégory Doré,2 Laleh Majlessi,3 Marie-Madeleine Gabellec,4 Arnaud Moris,5 Olivier Schwartz,5 James Di Santo,6 Ana Cumano,7 Claude Leclerc,3 and Françoise Lazarini1,2*

Neurovirologie et Régénération du Système Nerveux, Departement des Neurosciences,1 Repliement et Modélisation des Protéines, Departement de Biologie Structurale et Chimie,2 Biologie des Régulations Immunitaires, INSERM E352, Departement d'Immunologie,3 Perception et Mémoire Olfactive, Departement des Neurosciences,4 Virus et Immunité,5 Cytokines et Développement Lymphoïde,6 Développement des Lymphocytes, INSERM U668, Departement d'Immunologie, Institut Pasteur, 25 rue du Dr Roux, 75015 Paris, France7

Received 4 January 2006/ Accepted 28 February 2006

Dendritic cells (DC) are suspected to be involved in transmissible spongiform encephalopathies, including bovine spongiform encephalopathy (BSE). We detected the disease-specific, protease-resistant prion protein (PrPbse) in splenic DC purified by magnetic cell sorting 45 days after intraperitoneal inoculation of BSE prions in immunocompetent mice. We showed that bone marrow-derived DC (BMDC) from wild-type or PrP-null mice acquired both PrPbse and prion infectivity within 2 h of in vitro culture with a BSE inoculum. BMDC cleared PrPbse within 2 to 3 days of culture, while BMDC infectivity was only 10-fold diminished between days 1 and 6 of culture, suggesting that the infectious unit in BMDC is not removed at the same rate as PrPbse is removed from these cells. Bone marrow-derived plasmacytoid DC and bone marrow-derived macrophages (BMM) also acquired and degraded PrPbse when incubated with a BSE inoculum, with kinetics very similar to those of BMDC. PrPbse capture is probably specific to antigen-presenting cells since no uptake of PrPbse was observed when splenic B or T lymphocytes were incubated with a BSE inoculum in vitro. Lipopolysaccharide activation of BMDC or BMM prior to BSE infection resulted in an accelerated breakdown of PrPbse. Injected by the intraperitoneal route, BMDC were not infectious for alymphoid recombination-activated gene 20/common cytokine {gamma} chain-deficient mice, suggesting that these cells are not capable of directly propagating BSE infectivity to nerve endings.


* Corresponding author. Mailing address: Repliement et Modélisation des Protéines, Dpt Biologie Structurale et Chimie, Institut Pasteur, 25 rue du Dr Roux, 75015 Paris, France. Phone: 33 01 45 68 87 15. Fax: 33 01 45 68 87 68. E-mail: lazarini{at}pasteur.fr.


Journal of Virology, May 2006, p. 4656-4663, Vol. 80, No. 10
0022-538X/06/$08.00+0     doi:10.1128/JVI.80.10.4656-4663.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.




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