Some cellular and molecular aspects of prion neuroinvasion. Prion diseases such as scrapie manifest as afflictions of the central nervous system. After being taken up orally, prions must cross the epithelial barrier of the gut, probably via gastrointestinal Mcells (14). Thereafter, en route to the brain, they colonize several organ systems, taking advantage of multiple cell types to effect neuroinvasion. The experiments reported by Aucouturier and colleagues (12) indicate that dendritic cells (DCs) (but also lymphoid cells) isolated from spleens of prion-infected mice can induce disease when injected intravenously into immunodeficient Rag-1^–/– mice, suggesting a possible DC-dependent route to neuroinvasion. Other possible roles of dendritic cells in this disease pathway are discussed in the text.