Abstract
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 (PrPSc) comes into contact with native prion protein (PrPC) and changes its conformation to PrPSc. In many extraneurally inoculated models of prion disease this PrPC misfolding event occurs in lymphoid tissues prior to neuroinvasion. The primary objective of this study was to compare levels of total PrPC 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 PrPC levels. PrPC immunohistochemistry (IHC) of paraffin embedded tissue sections was performed to identify PrPC distribution in tissues of the lymphoreticular system. Nasal associated lymphoid tissue contained the highest amount of total PrPC followed by Peyer’s patches, mesenteric and submandibular lymph nodes, and spleen. The relative levels of PrPC expression in IHC processed tissue correlated strongly with the Western blot data, with high levels of PrPC corresponding with a higher percentage of PrPC positive B cell follicles. High levels of PrPC 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.
Highlights
The normal isoform of the prion protein (PrPC) is a highly conserved mammalian glycophosphatidylinositol linked membrane protein expressed in tissues throughout the body [1]
nasal associated lymphoid tissue (NALT) contained approximately 3, 5, and 6 fold the amount of PrPC per μg equivalent of tissue compared to Peyer’s patches (PP), mesenteric lymph nodes (MLN) and submandibular lymph nodes (SLN) respectively (Fig. 1B)
While NALT and SLN were both composed of two predominant forms of PrPC, PP total PrPC consisted of multiple truncated forms of PrPC which were between the molecular weights of full length and the truncated fragment C2
Summary
The normal isoform of the prion protein (PrPC) is a highly conserved mammalian glycophosphatidylinositol linked membrane protein expressed in tissues throughout the body [1]. PrPC is found in highest concentrations in the central nervous system, but is present in lower amounts in skeletal muscle, lung, intestine, autonomic ganglia, heart, and ovary [2, 3, 4]. Peripheral mucous associated lymphoid tissues, lymph nodes and spleen express PrPC, where it has been localized to follicular dendritic cells (FDCs), intraepithelial lymphocytes and dendritic cells [3, 5]. While the highly-conserved nature and wide distribution of PrPC suggest. The authors do not feel that this alters their adherence to PLOS ONE editorial policies and/or criteria
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