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

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.