{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T18:15:12Z","timestamp":1791137712829,"version":"4.1.0"},"reference-count":38,"publisher":"National Academy of Sciences","issue":"2","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2002,1,22]]},"abstract":"<jats:p>\n                    Variant Creutzfeldt\u2013Jakob disease and scrapie are typically initiated by extracerebral exposure to prions, and exhibit early prion accumulation in germinal centers. Follicular dendritic cells (FDCs), whose development and maintenance in germinal centers depends on tumor necrosis factor (TNF) and lymphotoxin (LT) signaling, are thought to be indispensable for extraneural prion pathogenesis. Here, we administered prions intraperitoneally to mice deficient for TNF and LT signaling components. LT\u03b1\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    , LT\u03b2\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    , LT\u03b2R\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    , and LT\u03b1\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    \u00d7 TNF\u03b1\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    mice resisted infection and contained no infectivity in spleens and lymph nodes (when present). However, TNFR1\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    , TNFR2\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    , and some TNF\u03b1\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    mice developed scrapie similarly to wild-type mice. High prion titers were detected in lymph nodes, but not spleens, of TNFR1\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    and TNF\u03b1\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    mice despite absence of FDCs and germinal centers. Transfer of TNFR1\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    fetal liver cells into lethally irradiated\n                    <jats:italic>Prnp<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>0\/0<\/jats:italic>\n                    <\/jats:sup>\n                    mice restored infectivity mainly in lymph nodes. Prion protein (PrP) colocalized with a minority of macrophages in tumor necrosis factor receptor (TNFR) 1\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    lymph nodes. Therefore, prion pathogenesis can be restricted to lymphoreticular subcompartments, and mature follicular dendritic cells are dispensable for this process. Macrophage subsets are plausible candidates for lymphoreticular prion pathogenesis and neuroinvasion in the absence of FDCs, and may represent a novel target for postexposure prophylaxis.\n                  <\/jats:p>","DOI":"10.1073\/pnas.022626399","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T10:36:44Z","timestamp":1027679804000},"page":"919-924","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":109,"title":["Lymph nodal prion replication and neuroinvasion in mice devoid of follicular dendritic cells"],"prefix":"10.1073","volume":"99","author":[{"given":"Marco","family":"Prinz","sequence":"first","affiliation":[{"name":"Institute of Neuropathology, University Hospital of Zurich, Schmelzbergstrasse 12, CH-8091 Zurich, Switzerland; Institute of Neurology, Humboldt- University (Charit\u00e9) Berlin, Schumannstrasse 20\/21, D-10098 Berlin, Germany; Laboratory for Special Techniques, Department of Pathology, University Hospital of Zurich, Schmelzbergstrasse 12, CH-8091 Zurich, Switzerland; and Institute of Microbiology, Immunology and Hygiene, Technical University of Munich, Trogerstrasse 9, D-81675 Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabio","family":"Montrasio","sequence":"additional","affiliation":[{"name":"Institute of Neuropathology, University Hospital of Zurich, Schmelzbergstrasse 12, CH-8091 Zurich, Switzerland; Institute of Neurology, Humboldt- University (Charit\u00e9) Berlin, Schumannstrasse 20\/21, D-10098 Berlin, Germany; Laboratory for Special Techniques, Department of Pathology, University Hospital of Zurich, Schmelzbergstrasse 12, CH-8091 Zurich, Switzerland; and Institute of Microbiology, Immunology and Hygiene, Technical University of Munich, Trogerstrasse 9, D-81675 Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael A.","family":"Klein","sequence":"additional","affiliation":[{"name":"Institute of Neuropathology, University Hospital of Zurich, Schmelzbergstrasse 12, CH-8091 Zurich, Switzerland; Institute of Neurology, Humboldt- University (Charit\u00e9) Berlin, Schumannstrasse 20\/21, D-10098 Berlin, Germany; Laboratory for Special Techniques, Department of Pathology, University Hospital of Zurich, Schmelzbergstrasse 12, CH-8091 Zurich, Switzerland; and Institute of Microbiology, Immunology and Hygiene, Technical University of Munich, Trogerstrasse 9, D-81675 Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Petra","family":"Schwarz","sequence":"additional","affiliation":[{"name":"Institute of Neuropathology, University Hospital of Zurich, Schmelzbergstrasse 12, CH-8091 Zurich, Switzerland; Institute of Neurology, Humboldt- University (Charit\u00e9) Berlin, Schumannstrasse 20\/21, D-10098 Berlin, Germany; Laboratory for Special Techniques, Department of Pathology, University Hospital of Zurich, Schmelzbergstrasse 12, CH-8091 Zurich, Switzerland; and Institute of Microbiology, Immunology and Hygiene, Technical University of Munich, Trogerstrasse 9, D-81675 Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Josef","family":"Priller","sequence":"additional","affiliation":[{"name":"Institute of Neuropathology, University Hospital of Zurich, Schmelzbergstrasse 12, CH-8091 Zurich, Switzerland; Institute of Neurology, Humboldt- University (Charit\u00e9) Berlin, Schumannstrasse 20\/21, D-10098 Berlin, Germany; Laboratory for Special Techniques, Department of Pathology, University Hospital of Zurich, Schmelzbergstrasse 12, CH-8091 Zurich, Switzerland; and Institute of Microbiology, Immunology and Hygiene, Technical University of Munich, Trogerstrasse 9, D-81675 Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bernhard","family":"Odermatt","sequence":"additional","affiliation":[{"name":"Institute of Neuropathology, University Hospital of Zurich, Schmelzbergstrasse 12, CH-8091 Zurich, Switzerland; Institute of Neurology, Humboldt- University (Charit\u00e9) Berlin, Schumannstrasse 20\/21, D-10098 Berlin, Germany; Laboratory for Special Techniques, Department of Pathology, University Hospital of Zurich, Schmelzbergstrasse 12, CH-8091 Zurich, Switzerland; and Institute of Microbiology, Immunology and Hygiene, Technical University of Munich, Trogerstrasse 9, D-81675 Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Klaus","family":"Pfeffer","sequence":"additional","affiliation":[{"name":"Institute of Neuropathology, University Hospital of Zurich, Schmelzbergstrasse 12, CH-8091 Zurich, Switzerland; Institute of Neurology, Humboldt- University (Charit\u00e9) Berlin, Schumannstrasse 20\/21, D-10098 Berlin, Germany; Laboratory for Special Techniques, Department of Pathology, University Hospital of Zurich, Schmelzbergstrasse 12, CH-8091 Zurich, Switzerland; and Institute of Microbiology, Immunology and Hygiene, Technical University of Munich, Trogerstrasse 9, D-81675 Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adriano","family":"Aguzzi","sequence":"additional","affiliation":[{"name":"Institute of Neuropathology, University Hospital of Zurich, Schmelzbergstrasse 12, CH-8091 Zurich, Switzerland; Institute of Neurology, Humboldt- University (Charit\u00e9) Berlin, Schumannstrasse 20\/21, D-10098 Berlin, Germany; Laboratory for Special Techniques, Department of Pathology, University Hospital of Zurich, Schmelzbergstrasse 12, CH-8091 Zurich, Switzerland; and Institute of Microbiology, Immunology and Hygiene, Technical University of Munich, Trogerstrasse 9, D-81675 Munich, 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