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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 [OPEN ACCESS]
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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

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