Dendritic cells and oral transmission of prion diseases

Abstract

Abstract Transmissible spongiform encephalopathies (scrapie, BSE, Kuru) develop as central nervous system (CNS) diseases after long incubation periods, and many of which may arise following the consumption of infected material. The infectious agent is thought to be a misfolded form (scrapie associated PrP (PrPSc)) of a normal host protein (cellular isoform of PrP (PrPC)), which is relatively resistant to proteolytic degradation and which serves as a template, directing host prion protein (PrP) to accumulate in the misfolded form. Animal experiments have shown that CNS disease is preceded by a period in which the agent accumulates in secondary lymphoid organs (Peyer's patches (PP), lymph nodes, spleen), particularly follicular dendritic cells (FDCs) in the B cell areas of these organs. How the agent is transmitted from the intestinal lumen to the FDCs is largely unknown. Dendritic cells (DCs, cells quite distinct from FDCs) are cells that are specialised to acquire antigens from peripheral tissues and to transport them to secondary lymphoid organs for presentation to T and B lymphocytes. We have shown that DCs can acquire PrPSc from the intestinal lumen and deliver it to mesenteric lymph nodes. In this review we discuss the different stages involved in the migration of PrPSc from the intestine to FDCs and consider the different stages and barriers involved in this process. We conclude that transport of the causative agent, using PrPSc as a biomarker, from the intestine to FDCs is a very inefficient process, which may help to account for the apparent low frequency of individuals who have consumed infected material that go on to develop clinical disease.