Does gastrointestinal microflora influence prion disease susceptibility or kinetics?

Completed Research Project

Title / Titel: Does gastrointestinal microflora influence prion disease susceptibility or kinetics?

Summary / Zusammenfassung: Prion ingestion is likely the natural route of transmission for many of the prion diseases, including BSE in cattle, scrapie in sheep and goats, kuru in humans, and chronic wasting disease in deer and elk. Little is known regarding the initial stages of prion entry, ie, prion uptake in the gastrointestinal tract, although studies in our laboratory have demonstrated that M cells play a role (Heppner et al., 2001). Bacterial microflora can influence the balance between effector and regulatory T cell components of the mucosal immune system. Therefore, an altered microbiota could disturb this balance, and result in inflammation and altered prion uptake and amplification by lymphoid cells. Additionally, derangement of the gastrointestinal microbiota may enhance prion transport across the mucosal barrier. Germ free mice have a thinner mucosal epithelium with increased permeability and a decreased number of M cells.
We hope to determine the potential effects of (1) an absence of microflora (germ free mice) on the incubation period of prion disease and (2) broad spectrum antibiotics which destroy gastrointestinal microflora.

Project Leadership and Contacts / Projektleitung und Kontakte

Christina Sigurdson (Project Leader)	christina.sigurdson@usz.ch
Prof. Adriano Aguzzi	adriano@pathol.uzh.ch

Other Links to external Webpages: http://www.uzh.ch/pathol/neuropathologie/d/index.html

Funding Source(s) / Unterstützt durch: Others
NIH K08 Mentored Clinical Scientist Development Award

In Collaboration with / In Zusammenarbeit mit

Irène Corthesy, Nestec Research Center	Switzerland
Prof. Andrew MacPherson, Experimental Immunology Institute, University Hospital of Zürich	Switzerland