Student Researcher Colorado State University Fort Collins, Colorado, United States
Introduction/Rationale: Prion protein (PrPC) is constitutively expressed in mammalian tissues with the highest concentration in neuronal and brain tissues. Although the function of PRPC remains unclear, PrPC can misfold into the pathogenic form (PrPSc), which induces conversion of other normal proteins, leading to aggregation, cell damage, and eventual onset of neurodegenerative disease. While later stages of prion pathogenesis are well characterized, the early immunological events following peripheral exposure remain poorly understood. We hypothesize that antigen-presenting cells (APCs) facilitate prion trafficking to secondary lymphoid organs shortly after exposure.
Methods: To identify the tissues involved and characterize the role of immune cells, muntjac deer were inoculated with prion-positive brain homogenate labeled with the fluorescent dye, Carboxyfluorescein succinimidyl ester (CFSE) and euthanized 1 hour post inoculation.
Results: Flow cytometric analysis revealed CFSE-positive cell populations that costained with B cell and macrophage markers in the spleen and draining lymph nodes, suggesting immune-mediated uptake and transport of prion material. Ongoing analysis utilizing multiplex immunofluorescence and prion amplification assays will further characterize tissue localization and cellular interactions involved with prion uptake and early deposition.
Conclusion: These data provide insights that will reveal mechanisms of early intra-host prion dissemination and potential targets to help in the development of strategies to mitigate prion and other neurodegenerative diseases.
