Characterization of the role of dendritic cells in prion transfer to primary neurons
| Autor: | Chiara Zurzolo, Maddalena Costanzo, Christelle Langevin, Odile Richard-Le Goff, Karine Gousset |
|---|---|
| Přispěvatelé: | Trafic membranaire et Pathogénèse, Institut Pasteur [Paris], Dipartimento di Biologia e Patologia Cellulare e Molecolare, Università di Napoli 'Federico II', Università degli studi di Napoli Federico II, KG is supported by the Pasteur Foundation Fellowship Program and MC is supported by a fellowship from the Ministère de Education Nationale et de la Recherche., ANR-09-BLAN-0122,Priontraf(2009), European Project: 34002,STRAINBARRIER, European Project: 222887,EC:FP7:KBBE,FP7-KBBE-2007-2A,PRIORITY(2009), Institut Pasteur [Paris] (IP), University of Naples Federico II = Università degli studi di Napoli Federico II, Langevin, C., Gousset, K., Costanzo, M., Richard Le Goff, O, Zurzolo, Chiara |
| Rok vydání: | 2010 |
| Předmět: |
Gene isoform
Nervous system Time Factors PrPSc Proteins Prions animal diseases Central nervous system Bone Marrow Cells Biology Biochemistry 03 medical and health sciences Mice Prion infection Prion infectivity medicine Animals Molecular Biology Cells Cultured 030304 developmental biology Neurons 0303 health sciences Transmissible spongiform encephalopathy Catabolism 030302 biochemistry & molecular biology Life Sciences Cell Biology Dendritic cell Dendritic Cells medicine.disease Virology Endocytosis Cell biology nervous system diseases Mice Inbred C57BL Protein Transport medicine.anatomical_structure nervous system [SDV.IMM]Life Sciences [q-bio]/Immunology [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC] Protein Processing Post-Translational |
| Zdroj: | Biochemical Journal Biochemical Journal, Portland Press, 2010, 431 (2), pp.189-198. ⟨10.1042/BJ20100698⟩ Biochemical Journal, 2010, 431 (2), pp.189-198. ⟨10.1042/BJ20100698⟩ |
| ISSN: | 1470-8728 0264-6021 |
| DOI: | 10.1042/BJ20100698⟩ |
| Popis: | International audience; Transmissible spongiform encephalopathies (TSEs) are neurodegenerative diseases caused by pathogenic isoforms (PrPSc) of the host-encoded cellular prion protein (PrPc). After consumption of contaminated food, PrPSc deposits rapidly accumulate in lymphoid tissues before invasion of the central nervous system (CNS). However the mechanisms of prion spreading from the periphery to the nervous system are still unclear. In this study, we investigated the role of dendritic cells (DCs) in the spreading of prion infection to neuronal cells. First, we determined that bone-marrow derived dendritic cells (BMDCs) rapidly uptake PrPSc after exposure to infected brain homogenate. Next, we observed a progressive catabolism of the internalized prion aggregates. Similar experiments performed with BMDCs isolated from knock-out (KO) or mice over-expressing PrP (tga20) indicate that both PrPSc uptake and catabolism are independent of PrPc expression in these cells. Finally, using co-cultures of prion-loaded BMDCs and cerebellar neurons, we characterized the transfer of the prion protein and the resulting infection of the neuronal cultures. Interestingly, the transfer of PrPSc was triggered by direct cell-to-cell contact. As a consequence, BMDCs kept the prion protein when cultured alone and no transfer to the recipient neurons was observed when a filter separated the two cultures or when neurons were exposed to the BMDCs conditioned media. Additionally, fixed BMDCs also failed to transfer prion infectivity to neurons suggesting an active transport of prion aggregates, in accordance with a role of tunnelling nanotubes (TNTs) observed in the co-cultures. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|