Bacterial colitis increases susceptibility to oral prion disease.
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. We report 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.
Sigurdson
Christina J
CJ
Institute of Neuropathology, University Hospital of Zürich, Zürich, Switzerland.
Heikenwalder
Mathias
M
Manco
Giuseppe
G
Barthel
Manja
M
Schwarz
Petra
P
Stecher
Bärbel
B
Krautler
Nike J
NJ
Hardt
Wolf-Dietrich
WD
Seifert
Burkhardt
B
MacPherson
Andrew J S
AJ
Corthesy
Irène
I
Aguzzi
Adriano
A
D000818:Animals; D002432:Cecum / Q000378:metabolism; D004198:Disease Susceptibility; D004760:Enterocolitis / Q000150:complications* / Q000382:microbiology; D051379:Mice; D008810:Mice, Inbred C57BL; D009059:Mouth Diseases / Q000150:complications* / Q000378:metabolism; D018621:PrPC Proteins / Q000378:metabolism; D018620:PrPSc Proteins / Q000378:metabolism; D017096:Prion Diseases / Q000150:complications* / Q000378:metabolism; D011328:Prions / Q000378:metabolism / Q000472:pathogenicity*; D012307:Risk Factors; D012480:Salmonella Infections / Q000150:complications* / Q000382:microbiology; D012486:Salmonella typhimurium / Q000235:genetics / Q000472:pathogenicity*; D012608:Scrapie / Q000150:complications / Q000378:metabolism; D013047:Specific Pathogen-Free Organisms
D018621:PrPC Proteins; D018620:PrPSc Proteins; D011328:Prions