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Positioning of follicular dendritic cells within the spleen controls prion neuroinvasion

Official URL:https://doi.org/10.1038/nature02072
PubMed:View item in PubMed
Creators Name:Prinz, M. and Heikenwalder, M. and Junt, T. and Schwarz, P. and Glatzel, M. and Heppner, F.L. and Fu, Y.X. and Lipp, M. and Aguzzi, A.
Journal Title:Nature
Journal Abbreviation:Nature
Volume:425
Number:6961
Page Range:957-962
Date:30 October 2003
Keywords:Bone Marrow Transplantation, Chemokine Receptors, Chimera, Cytokine Receptors, Dendritic Cells, Gene Deletion, Kinetics, Knockout Mice, Lymphotoxin Beta Receptor, Prions, Scrapie, Signal Transduction, Spinal Cord, Spleen, Sympathetic Nervous System, Tumor Necrosis Factor Receptors, Animals, Mice
Abstract:Peripheral infection is the natural route of transmission in most prion diseases. Peripheral prion infection is followed by rapid prion replication in lymphoid organs, neuroinvasion and progressive neurological disease. Both immune cells and nerves are involved in pathogenesis, but the mechanisms of prion transfer from the immune to the nervous system are unknown. Here we show that ablation of the chemokine receptor CXCR5 juxtaposes follicular dendritic cells (FDCs) to major splenic nerves, and accelerates the transfer of intraperitoneally administered prions into the spinal cord. Neuroinvasion velocity correlated exclusively with the relative locations of FDCs and nerves: transfer of CXCR5-/- bone marrow to wild-type mice induced perineural FDCs and enhanced neuroinvasion, whereas reciprocal transfer to CXCR5-/- mice abolished them and restored normal efficiency of neuroinvasion. Suppression of lymphotoxin signalling depleted FDCs, abolished splenic infectivity, and suppressed acceleration of pathogenesis in CXCR5 -/- mice. This suggests that prion neuroimmune transition occurs between FDCs and sympathetic nerves, and relative positioning of FDCs and nerves controls the efficiency of peripheral prion infection.
ISSN:0028-0836
Publisher:Nature Publishing Group (U.K.)
Item Type:Article

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