Letter abstract
Nature Cell Biology 11, 328 - 336 (2009)
Published online: 8 February 2009 | doi:10.1038/ncb1841
Prions hijack tunnelling nanotubes for intercellular spread
Karine Gousset1,7, Edwin Schiff1,2,7, Christelle Langevin1, Zrinka Marijanovic1, Anna Caputo1,3, Duncan T. Browman1, Nicolas Chenouard4, Fabrice de Chaumont4, Angelo Martino5, Jost Enninga6, Jean-Christophe Olivo-Marin4, Daniela Männel2 & Chiara Zurzolo1,3
In variant Creutzfeldt–Jakob disease, prions (PrPSc) enter the body with contaminated foodstuffs and can spread from the intestinal entry site to the central nervous system (CNS) by intercellular transfer from the lymphoid system to the peripheral nervous system (PNS)1. Although several means2, 3, 4 and different cell types5, 6, 7 have been proposed to have a role, the mechanism of cell-to-cell spreading remains elusive. Tunnelling nanotubes (TNTs) have been identified between cells8, 9, 10, 11, 12, both in vitro and in vivo10, 11, 13, and may represent a conserved means of cell-to-cell communication14, 15, 16. Here we show that TNTs allow transfer of exogenous and endogenous PrPSc between infected and naive neuronal CAD cells17. Significantly, transfer of endogenous PrPSc aggregates was detected exclusively when cells chronically infected with the 139A mouse prion strain were connected to mouse CAD cells by means of TNTs, identifying TNTs as an efficient route for PrPSc spreading in neuronal cells. In addition, we detected the transfer of labelled PrPSc from bone marrow-derived dendritic cells to primary neurons connected through TNTs. Because dendritic cells can interact with peripheral neurons in lymphoid organs, TNT-mediated intercellular transfer would allow neurons to transport prions retrogradely to the CNS1. We therefore propose that TNTs are involved in the spreading of PrPSc within neurons in the CNS and from the peripheral site of entry to the PNS by neuroimmune interactions with dendritic cells.
- Unité de Trafic Membranaire et Pathogénèse, Institut Pasteur, 25 rue du Dr Roux, 75724 Paris Cedex 15, France.
- Department of Immunology, University of Regensburg, F.-J.-Strauss-Allee, 93042 Regensburg, Germany.
- Dipartimento di Biologia e Patologia Cellulare e Molecolare, Università degli Studi di Napoli 'Federico II', via Pansini 5, 80131 Naples, Italy.
- Unité d'Analyse d'Images Quantitative, Institut Pasteur, 25 rue du Dr Roux, 75724 Paris Cedex 15, France.
- Unité de recherché de Génétique Mycobactérienne, Institut Pasteur, 25 rue du Dr Roux, 75724 Paris Cedex 15, France.
- Groupe "Dynamique des interactions hôte-pathogène", Institut Pasteur, 25 rue du Dr Roux, 75724 Paris Cedex 15, France.
- These authors contributed equally to this work.
Correspondence to: Chiara Zurzolo1,3 e-mail: zurzolo@unina.it; e-mail: zurzolo@pasteur.fr
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