Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Heikenwalder, M; Kurrer, MO; Margalith, I; Kranich, J; Zeller, N; Haybaeck, J; Polymenidou, M; Matter, M; Bremer, J; Jackson, WS; Lindquist, S; Sigurdson, CJ; Aguzzi, A.
Lymphotoxin-dependent prion replication in inflammatory stromal cells of granulomas.
Immunity. 2008; 29(6): 998-1008.
Doi: 10.1016/j.immuni.2008.10.014
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- Co-Autor*innen der Med Uni Graz
- Haybäck Johannes
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- Abstract:
- Prior to invading the nervous system, prions frequently colonize lymphoid organs and sites of inflammatory lymphoneogenesis, where they colocalize with Mfge8+ follicular dendritic cells (FDCs). Here, we report that soft-tissue granulomas, a frequent feature of chronic inflammation, expressed the cellular prion protein (PrPC, encoded by Prnp) and the lymphotoxin receptor (LTbetaR), even though they lacked FDCs and did not display lymphoneogenesis. After intraperitoneal prion inoculation, granulomas of Prnp(+/+) mice, but not Prnp(-/-) granulomas or unaffected Prnp(+/+) skin, accumulated prion infectivity and disease-associated prion protein. Bone-marrow transfers between Prnp(+/+) and Prnp(-/-) mice and administration of lymphotoxin signaling antagonists indicated that prion replication required radioresistant PrPC-expressing cells and LTbetaR signaling. Granulomatous PrPC was mainly expressed by stromal LTbetaR+ mesenchymal cells that were absent from unaffected subcutis. Hence, granulomas can act as clinically silent reservoirs of prion infectivity. Furthermore, lymphotoxin-dependent prion replication can occur in inflammatory stromal cells that are distinct from FDCs.
- Find related publications in this database (using NLM MeSH Indexing)
- Animals -
- Dendritic Cells, Follicular - immunology Dendritic Cells, Follicular - metabolism
- Granuloma - genetics Granuloma - immunology Granuloma - pathology
- Lymphotoxin beta Receptor - immunology Lymphotoxin beta Receptor - metabolism
- Lymphotoxin-alpha - immunology Lymphotoxin-alpha - metabolism
- Mice -
- Mice, Inbred C57BL -
- Mice, Knockout -
- Prions - genetics Prions - metabolism
- Stromal Cells - immunology Stromal Cells - metabolism