Nasal Associated Lymphoid Tissue of the Syrian Golden Hamster Expresses High Levels of PrP(C)

The key event in the pathogenesis of the transmissible spongiform encephalopathies is a template-dependent misfolding event where an infectious isoform of the prion protein (PrP(Sc)) comes into contact with native prion protein (PrP(C)) and changes its conformation to PrP(Sc). In many extraneurally inoculated models of prion disease this PrP(C) misfolding event occurs in lymphoid tissues prior to neuroinvasion. The primary objective of this study was to compare levels of total PrP(C) in hamster lymphoid tissues involved in the early pathogenesis of prion disease. Lymphoid tissues were collected from golden Syrian hamsters and Western blot analysis was performed to quantify PrP(C) levels. PrP(C) immunohistochemistry (IHC) of paraffin embedded tissue sections was performed to identify PrP(C) distribution in tissues of the lymphoreticular system. Nasal associated lymphoid tissue contained the highest amount of total PrP(C) followed by Peyer’s patches, mesenteric and submandibular lymph nodes, and spleen. The relative levels of PrP(C) expression in IHC processed tissue correlated strongly with the Western blot data, with high levels of PrP(C) corresponding with a higher percentage of PrP(C) positive B cell follicles. High levels of PrP(C) in lymphoid tissues closely associated with the nasal cavity could contribute to the relative increased efficiency of the nasal route of entry of prions, compared to other routes of infection.