Role of the CD8 + Dendritic Cell Subset in Transmission of Prions

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Abstract
Controversial results have been observed in mouse models regarding the role of lymphoid tissues in prion pathogenesis. To investigate the role of dendritic cells (DC), we used a transgenic mouse model. In this model (CD11c-N17Rac1), a significant reduction of CD8+ CD11chi DC has been described, and the remaining CD8+ DC demonstrate a reduced capacity for the uptake of apoptotic cells. After intraperitoneal prion infection, significantly longer incubation times were observed in CD11c-N17Rac1 mice than in controls, indicating that a defect in CD8+ CD11chi DC significantly impedes neuroinvasion after intraperitoneal infection. In contrast, no distinct differences were observed between CD11c-N17Rac1 mice and controls after oral infection. This provides evidence that oral and intraperitoneal prion infections differ in lymphoreticular requirements.