Positioning of follicular dendritic cells within the spleen controls prion neuroinvasion

Marco Prinz, Mathias Heikenwalder, Tobias Junt, Petra Schwarz, Markus Glatzel, Frank L. Heppner, Yang-Xin Fu, Martin Lipp and Adriano Aguzzi ()
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Marco Prinz: University Hospital of Zürich
Mathias Heikenwalder: University Hospital of Zürich
Tobias Junt: University Hospital of Zürich
Petra Schwarz: University Hospital of Zürich
Markus Glatzel: University Hospital of Zürich
Frank L. Heppner: University Hospital of Zürich
Yang-Xin Fu: The University of Chicago
Martin Lipp: Max Delbrück Center for Molecular Medicine (MDC)
Adriano Aguzzi: University Hospital of Zürich

Nature, 2003, vol. 425, issue 6961, 957-962

Abstract: Abstract Peripheral infection is the natural route of transmission in most prion diseases1. Peripheral prion infection is followed by rapid prion replication in lymphoid organs, neuroinvasion2 and progressive neurological disease. Both immune cells and nerves are involved in pathogenesis3,4, 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.

Date: 2003
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DOI: 10.1038/nature02072

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