title: Processing of the bovine spongiform encephalopathy-specific prion protein by dendritic cells.
abstract: 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 (PrP(bse)) 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 PrP(bse) and prion infectivity within 2 h of in vitro culture with a BSE inoculum. BMDC cleared PrP(bse) 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 PrP(bse) is removed from these cells. Bone marrow-derived plasmacytoid DC and bone marrow-derived macrophages (BMM) also acquired and degraded PrP(bse) when incubated with a BSE inoculum, with kinetics very similar to those of BMDC. PrP(bse) capture is probably specific to antigen-presenting cells since no uptake of PrP(bse) 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 PrP(bse). Injected by the intraperitoneal route, BMDC were not infectious for alymphoid recombination-activated gene 2(0)/common cytokine gamma chain-deficient mice, suggesting that these cells are not capable of directly propagating BSE infectivity to nerve endings.
authors.affiliation: Neurovirologie et Régénération du Système Nerveux, Department de Neurosciences, Repliement et Modélisation des Protéines, Dpt Biologie Structurale et Chimie, Biologie des Régulations Immunaires, INSERM E352, 75015 Paris, France.
authors.forename: Catherine
authors.initials: C
authors.lastname: Rybner-Barnier
authors.forename: Catherine
authors.initials: C
authors.lastname: Jacquemot
authors.forename: Céline
authors.initials: C
authors.lastname: Cuche
authors.forename: Grégory
authors.initials: G
authors.lastname: Doré
authors.forename: Laleh
authors.initials: L
authors.lastname: Majlessi
authors.forename: Marie-Madeleine
authors.initials: MM
authors.lastname: Gabellec
authors.forename: Arnaud
authors.initials: A
authors.lastname: Moris
authors.forename: Olivier
authors.initials: O
authors.lastname: Schwartz
authors.forename: James
authors.initials: J
authors.lastname: Di Santo
authors.forename: Ana
authors.initials: A
authors.lastname: Cumano
authors.forename: Claude
authors.initials: C
authors.lastname: Leclerc
authors.forename: Françoise
authors.initials: F
authors.lastname: Lazarini
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000378:metabolism; D002417:Cattle; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000378:metabolism*; D016643:Encephalopathy, Bovine Spongiform / Q000378:metabolism* / Q000503:physiopathology; D053631:Interleukin Receptor Common gamma Subunit; D008264:Macrophages / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D011328:Prions / Q000378:metabolism*; D011499:Protein Processing, Post-Translational; D018123:Receptors, Interleukin / Q000172:deficiency / Q000235:genetics; D013154:Spleen / Q000166:cytology / Q000378:metabolism
chemical_list: C507942:Il2rg protein, mouse; D053631:Interleukin Receptor Common gamma Subunit; D011328:Prions; D018123:Receptors, Interleukin