Intestinal Transmission of Prions and Role of Exosomes in Enterocytes

摘要

Infectious prion diseases include Kuru and its variant, Creutzfeldt-Jakob disease, in humans, scrapie in sheep, and bovine spongiform encephalopathy in cattle. In these diseases, the pathogenic prion protein (PrP~(Sc)) enters the host through the gastrointestinal tract and migrates to the central nervous system, where PrP~(Sc) induces characteristic pathological changes. The mechanisms underlying this intercellular transfer are not fully understood. After oral administration, PrP~(Sc) withstands the digestive process and may be incorporated by microfold cells (M cells) or villous columnar epithelial cells in the intestine. Based on Western Blot with specific markers, liquid chromatography, and morphological analysis, the cellular prion protein (PrP~(C)) and PrP~(Sc) in the cells are associated with exosomes, membranous vesicles that are secreted upon fusion of multivesicular endosomes with the plasma membranes. Exosomes may play a role in PrP transportation through intestinal epithelium. Cells may exploit the nature of endosome-derived exosomes to communicate with each other in normal and pathological situations, providing for a novel route of cell-to-cell communication and therefore of pathogen transmission in the intestinal epithelium. In addition, since most bovine spongiform encephalopathy cases were exposed to the agent in the first six months of life, developmental alteration of the intestinal defense and immune system may also be involved in the susceptibility to infection.