Prions hijack tunnelling nanotubes for intercellular spread

被引:476
作者
Gousset, Karine [1 ]
Schiff, Edwin [1 ,2 ]
Langevin, Christelle [1 ]
Marijanovic, Zrinka [1 ]
Caputo, Anna [1 ,3 ]
Browman, Duncan T. [1 ]
Chenouard, Nicolas [4 ]
de Chaumont, Fabrice [4 ]
Martino, Angelo [5 ]
Enninga, Jost [6 ]
Olivo-Marin, Jean-Christophe [4 ]
Maennel, Daniela [2 ]
Zurzolo, Chiara [1 ,3 ]
机构
[1] Inst Pasteur, Unite Traf Membranaire & Pathogenese, F-75724 Paris 15, France
[2] Univ Regensburg, Dept Immunol, D-93042 Regensburg, Germany
[3] Univ Naples Federico 2, Dipartimento Biol & Patol Cellulare & Mol, I-80131 Naples, Italy
[4] Inst Pasteur, Unite Anal Images Quantitat, F-75724 Paris 15, France
[5] Inst Pasteur, Unite Rech Genet Mycobacterienne, F-75724 Paris 15, France
[6] Inst Pasteur, Grp Dynam Interact Hote Pathogene, F-75724 Paris 15, France
关键词
FOLLICULAR DENDRITIC CELLS; MEMBRANE NANOTUBES; IMMUNE CELLS; PEYERS-PATCHES; NEURONAL CELLS; IMAGINAL DISCS; CUTTING EDGE; T-CELLS; IN-VIVO; SCRAPIE;
D O I
10.1038/ncb1841
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
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 means(2-4) and different cell types(5-7) have been proposed to have a role, the mechanism of cell-to-cell spreading remains elusive. Tunnelling nanotubes (TNTs) have been identified between cells(8-12), both in vitro and in vivo(10,11,13), and may represent a conserved means of cell-to-cell communication(14-16). Here we show that TNTs allow transfer of exogenous and endogenous PrPSc between infected and naive neuronal CAD cells(17). 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.
引用
收藏
页码:328 / U232
页数:28
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