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Spreading of prions from the immune to the peripheral nervous system: a potential implication of dendritic cells

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Abstract

The implication of dendritic cells (DCs) in the peripheral spreading of prions has increased in the last few years. It has been recently described that DCs can transmit prions to primary neurons from the central nervous system. In order to improve the understanding of the earliest steps of prion peripheral neuroinvasion, we studied, using an in vitro model, the effect of exposing primary peripheral neurons to scrapie-infected lymphoid cells. Thanks to this system, there is evidence that bone marrow dendritic cells (BMDCs) are in connection with neurites of peripheral neurons via cytoplasmic extensions. BMDCs are competent to internalize prions independently from the expression of cellular prion protein (PrPC) and have the capacity to transmit detergent-insoluble, relatively proteinase K-resistant prion protein (PrPSc) to peripheral neurons after 96 h of coculture. Furthermore, we confirmed the special status of the peripheral nervous system in front of prion diseases. Contrary to central neurons, PrPSc infection does not disturb survival and neurite outgrowth. Our model demonstrates that PrPSc-loaded dendritic cells and peripheral nerve fibers that are included in neuroimmune interfaces can initiate and spread prion neuroinvasion.

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Acknowledgments

This study was supported by Région Wallone and EU research Immuno TSE project number QLK5-CT-2002-01044. Primary cultures of BMDCs from B6 mice and PrP−/− mice were kindly provided by Christian Villiers, Inserm U823, La Tronche. SAF antibodies were kindly provided by Jacques Grassi CEA Saclay, Gif-sur-Yvette.

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Authors and Affiliations

  1. Human Histology, Immunology Center, Faculty of Medicine, University of Liège, C.H.U., Avenue de l’hôpital, Tour de pharmacie +4, 4000, Liège, Belgium

    Gauthier Dorban, Valérie Defaweux & Ernst Heinen

  2. Life Sciences Research Unit, Faculty of Science, Technology and Communication, University of Luxembourg, Campus Limpertsberg, 162a, avenue de la Faïencerie, 1511, Luxembourg, Luxembourg

    Gauthier Dorban

  3. Department of Morphology-Pathology, Animal Histology, Faculty of Veterinary Medicine, University of Liège, Boulevard de Colonster, 4000, Liège, Belgium

    Nadine Antoine

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  1. Gauthier Dorban
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  2. Valérie Defaweux
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  4. Nadine Antoine
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Correspondence to Gauthier Dorban.

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418_2010_687_MOESM1_ESM.tif

PrPSc accumulation in peripheral neurons and BMDCs cocultured for 96 hours and cultured separately for 6 hours (cell-blot crude). (TIFF 3120 kb)

418_2010_687_MOESM2_ESM.tif

PrPSc accumulation in peripheral neurons and BMDCs cocultured for 96 hours and cultured separately for 6 hours (cell-blot converted with ImageJ). (TIFF 2106 kb)

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Dorban, G., Defaweux, V., Heinen, E. et al. Spreading of prions from the immune to the peripheral nervous system: a potential implication of dendritic cells. Histochem Cell Biol 133, 493–504 (2010). https://doi.org/10.1007/s00418-010-0687-9

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