Sigurdson
Fakultäten » Medizinische Fakultät » Neuropathologie, Institut für » Prof. Dr. Adriano Aguzzi » Sigurdson
Completed research project
| Title / Titel | Investigation of sheep scrapie transmission via milk from the inflamed mammary gland | ||||
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| Abstract (PDF, 14 KB) | |||||
| Summary / Zusammenfassung | Recent findings have shown that chronic inflammation predisposes an organ to prion accumulation. Given the presence of follicular dendritic cell (FDC)-containing B cell follicles, pathogenic prions can accumulate in organs beyond the CNS and lymphoid system. Indeed, results from wild type and transgenic mouse models have demonstrated that chronic follicular inflammation supports infectious prion accumulation in the liver, pancreas, and kidney, and it is likely that any organ with lymphotoxin/tumor necrosis factor (LT/TNF)-induced FDC generation can accumulate pathogenic prions. As follicular inflammation is common in ruminants and in humans, ie, from infectious disease, follicular lymphoma, or immune-mediated disorders, it is possible that prions may silently accumulate in organs with chronic inflammation, and may contribute to prion transmission. Maedi-visna virus (MVV) is a common, chronic lentiviral infection in sheep that occurs throughout Europe, and causes a lymphoid follicular pneumonia, arthritis, and mastitis, and a demyelinating encephalomyelitis. The lymphoid follicles create an ideal environment for scrapie accumulation, and indeed, we have found sheep naturally infected with scrapie and MVV that have pathogenic prions (PrPSc) in the mammary gland. Infectious prions may be shed into the milk from sheep with MVV and scrapie co-infections, and could serve as a natural mechanism for scrapie transmission. We propose to investigate sheep which are experimentally infected with MVV and sheep scrapie. Our experimental aims are to determine whether: (1) a mastitic mammary gland harbors infectious prions in scrapie infected sheep, (2) milk from these sheep can transmit scrapie to uninfected lambs, and (3) a transgenic mouse with lymphoid follicular mastitis can be used to model scrapie transmission via milk to the mouse pups. Mastitic milk may serve as a conduit for sheep scrapie transmission, a finding which would enhance our understanding of scrapie transmission in sheep and also have broad-ranging implications for general prion transmission in body fluids from inflamed organs. |
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| Keywords / Suchbegriffe | TSE, prion pathogenesis, scrapie, inflammation, mastitis | ||||
| Project leadership and contacts / Projektleitung und Kontakte |
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| Other links to external web pages | http://www.neuropathologie.usz.ch/ | ||||
| Funding source(s) / Unterstützt durch |
Others DEFRA, UK |
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| In collaboration with / In Zusammenarbeit mit |
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| Duration of Project / Projektdauer | Sep 2005 to Aug 2008 |