Human Histology, Immunology Center, Faculty of Medicine, University of Liège, C.H.U., Avenue de l'hôpital, Tour de pharmacie +4, 4000, Liège, Belgium.
Histochem Cell Biol. 2010 May;133(5):493-504. doi: 10.1007/s00418-010-0687-9. Epub 2010 Mar 18.
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 (PrP(C)) and have the capacity to transmit detergent-insoluble, relatively proteinase K-resistant prion protein (PrP(Sc)) 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, PrP(Sc) infection does not disturb survival and neurite outgrowth. Our model demonstrates that PrP(Sc)-loaded dendritic cells and peripheral nerve fibers that are included in neuroimmune interfaces can initiate and spread prion neuroinvasion.
树突状细胞（DCs）在朊病毒的外周扩散中的作用在近几年得到了更多的关注。最近有研究描述了 DCs 可以将朊病毒从中枢神经系统传播到原代神经元。为了更好地理解朊病毒外周神经入侵的最初步骤，我们使用体外模型研究了将感染瘙痒病的淋巴样细胞暴露于原代周围神经元的影响。有证据表明，骨髓树突状细胞（BMDCs）通过细胞质延伸与周围神经元的神经突相连，这要归功于该系统。BMDCs 能够独立于细胞朊蛋白（PrP(C)）的表达内化朊病毒，并在共培养 96 小时后将去污剂不溶性、相对蛋白酶 K 抗性的朊病毒蛋白（PrP(Sc)）传递给周围神经元。此外，我们还证实了外周神经系统在朊病毒疾病面前的特殊地位。与中枢神经元相反，PrP(Sc)感染不会干扰存活和神经突生长。我们的模型表明，负载 PrP(Sc)的树突状细胞和包含在神经免疫界面中的周围神经纤维可以引发并传播朊病毒神经入侵。
