Abstract
A number of studies have suggested that macrophages, dendritic cells, and follicular dendritic cells play an important role in the propagation of PrPSc. Both accumulation and proteolysis of PrPSc have been demonstrated in peripheral macrophages. Macrophages may act as reservoirs for PrPSc particles if the cells die during transient PrPSc propagation. However, whether cell death plays a role in PrPSc propagation in macrophages remains unclear. In this study, we investigated the possibility of propagation and transmission of PrPSc between dead immune cells and living neural cells. We found that under specific conditions, transient PrPSc propagation occurs in dead cells, indicating that interaction between PrPC and PrPSc on plasma membrane lipid rafts might be important for PrPSc propagation. Co-culturing of killed donor PrPSc-infected macrophages with recipient N2a-3 neuroblastoma cells accelerated PrPSc transmission. Our results suggest that cell death may play an important role in PrPSc propagation, whereas transient PrPSc propagation in macrophages has little effect on PrPSc transmission.
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This work was supported by a grant (22380165) from the Ministry of Education, Culture, Sports, Science, and Technology and by a grant from the Ministry of Health, Labour, and Welfare of Japan.
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Takahashi, K., Inoshima, Y. & Ishiguro, N. Role of cell death in the propagation of PrPSc in immune cells. Arch Virol 160, 693–699 (2015). https://doi.org/10.1007/s00705-014-2320-z
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DOI: https://doi.org/10.1007/s00705-014-2320-z