Endoplasmic reticulum stress influences the localization of prion protein in the small intestine and mesenteric lymph nodes

Tunicamycin is an endoplasmic reticulum (ER) stressor that inhibits protein glycosylation and promotes ER stress. To better understand the localization and traffic of prion protein (PrP) in both basal and ER stress conditions, we evaluated the presence and relative expression of PrP in the intestinal compartments of normal and tunicamycin-treated mice. After tunicamycin treatment, the level of PrP was significantly increased in enterocytes and blind-ended villous lymphatic vessels (lacteals), but was decreased in M cells. These results suggested that intake from the gut and transfer into lymphoid compartments of basal PrP occurs largely through the M cell-Peyer?s patch-mesenteric lymph node axis, and also alternatively through the enterocyte-lacteal-mesenteric lymph node axis. In ER stress, the enterocyte-lacteal-mesenteric lymph node is the sole axis for PrP transmission. Results also indicated that germinal centers and high endothelial venules (HEVs) are the most prominent portal for entry of PrP in both basal and ER stressed conditions. We speculated that PrP may use alternative routes for entry into intestinal compartments according to the pathophysiological state and that the mechanism managing the routes of PrP could contribute to the development of new therapeutic strategies against prion diseases as well as ER stress-related intestinal disorders.