Oral Prion Neuroinvasion Occurs Independently of PrP C Expression in the Gut Epithelium

Abstract

The accumulation of orally acquired prions within Peyer's patches in the small intestine is essential for the efficient spread of disease to the brain. Little is known of how the prions initially establish infection within Peyer's patches. Some gastrointestinal pathogens utilize molecules, such as the cellular prion protein PrP C , expressed on gut epithelial cells to enter Peyer's patches. Acute mucosal inflammation can enhance PrP C expression in the intestine, implying the potential to enhance oral prion disease susceptibility. We used transgenic mice to determine whether the uptake of prions into Peyer's patches was dependent upon PrP C expression in the gut epithelium. We show that orally acquired prions can establish infection in Peyer's patches independently of PrP C expression in gut epithelial cells. Our data suggest that the magnitude of PrP C expression in the epithelium lining the small intestine is unlikely to be an important factor which influences oral prion disease susceptibility.