Skip to Main content Skip to Navigation
Journal articles

Prions hijack tunnelling nanotubes for intercellular spread.

Abstract : In variant Creutzfeldt-Jakob disease, prions (PrP(Sc)) 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). Although several means and different cell types have been proposed to have a role, the mechanism of cell-to-cell spreading remains elusive. Tunnelling nanotubes (TNTs) have been identified between cells, both in vitro and in vivo, and may represent a conserved means of cell-to-cell communication. Here we show that TNTs allow transfer of exogenous and endogenous PrP(Sc) between infected and naive neuronal CAD cells. Significantly, transfer of endogenous PrP(Sc) 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 PrP(Sc) spreading in neuronal cells. In addition, we detected the transfer of labelled PrP(Sc) 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 CNS. We therefore propose that TNTs are involved in the spreading of PrP(Sc) within neurons in the CNS and from the peripheral site of entry to the PNS by neuroimmune interactions with dendritic cells.
Document type :
Journal articles
Complete list of metadatas

https://hal-pasteur.archives-ouvertes.fr/pasteur-00368712
Contributor : Marie Lemesle <>
Submitted on : Tuesday, March 17, 2009 - 1:52:56 PM
Last modification on : Friday, September 18, 2020 - 2:52:03 PM

Links full text

Identifiers

Collections

Citation

Karine Gousset, Edwin Schiff, Christelle Langevin, Zrinka Marijanovic, Anna Caputo, et al.. Prions hijack tunnelling nanotubes for intercellular spread.. Nature Cell Biology, Nature Publishing Group, 2009, 11 (3), pp.328 - 336. ⟨10.1038/ncb1841⟩. ⟨pasteur-00368712⟩

Share

Metrics

Record views

440