Bacterial Colitis Increases Susceptibility to Oral Prion Disease

• Published in: The Journal of infectious diseases 2009-01, Vol.199 (2), p.243-252
• Main Authors: Sigurdson, Christina J., Heikenwalder, Mathias, Manco, Giuseppe, Barthel, Manja, Schwarz, Petra, Stecher, Bärbel, Krautler, Nike J., Hardt, Wolf-Dietrich, Seifert, Burkhardt, MacPherson, Andrew J. S., Corthesy, Irène, Aguzzi, Adriano
• Format: Article
• Language: English
• Subjects: Animals; Bacteria; Bacteriology; Biological and medical sciences; Cecum; Cecum - metabolism; Colitis; Creutzfeldt Jakob syndrome; Disease Susceptibility; Dosage; Enterocolitis - complications; Enterocolitis - microbiology; Fundamental and applied biological sciences. Psychology; Infections; Infectious diseases; Inflammation; Inoculation; Medical sciences; Mice; Mice, Inbred C57BL; Microbiology; Miscellaneous; Mouth Diseases - complications; Mouth Diseases - metabolism; Non conventional transmissible agents; Prion diseases; Prion Diseases - complications; Prion Diseases - metabolism; Prions; Prions - metabolism; Prions - pathogenicity; PrPC Proteins - metabolism; PrPSc Proteins - metabolism; Risk Factors; Salmonella; Salmonella Infections - complications; Salmonella Infections - microbiology; Salmonella typhimurium - genetics; Salmonella typhimurium - pathogenicity; Scrapie - complications; Scrapie - metabolism; Specific Pathogen-Free Organisms; Spleen
• ISSN: 0022-1899; 1537-6613
• DOI: 10.1086/595791

Dietary exposure to prion-contaminated materials has caused kuru and variant Creutzfeldt-Jakob disease in humans and transmissible spongiform encephalopathies (TSEs) in cattle, mink, and felines. The epidemiology of dietary prion infections suggests that host genetic modifiers and possibly exogenous cofactors may play a decisive role in determining disease susceptibility. However, few cofactors influencing susceptibility to prion infection have been identified. In the present study,we investigated whether colitis might represent one such cofactor.Were port that moderate colitis caused by an attenuated Salmonella strain more than doubles the susceptibility of mice to oral prion infection and modestly accelerates the development of disease after prion challenge. The prion protein was up-regulated in intestines and mesenteric lymph nodes of mice with colitis, providing a possible mechanism for the effect of colitis on the pathogenesis of prion disease. Therefore, moderate intestinal inflammation at the time of prion exposure may constitute one of the elusive risk factors underlying the development of TSE.