Positioning of follicular dendritic cells within the spleen controls prion neuroinvasion

被引:170
作者
Prinz, M
Heikenwalder, M
Junt, T
Schwarz, P
Glatzel, M
Heppner, FL
Fu, YX
Lipp, M
Aguzzi, A
机构
[1] Univ Zurich Hosp, Inst Neuropathol, CH-8091 Zurich, Switzerland
[2] Univ Zurich Hosp, Inst Expt Immunol, CH-8091 Zurich, Switzerland
[3] Univ Chicago, Dept Pathol, Chicago, IL 60637 USA
[4] Univ Chicago, Comm Immunol, Chicago, IL 60637 USA
[5] Max Delbruck Ctr Mol Med, Dept Mol Tumor Genet & Immunogenet, D-13092 Berlin, Germany
关键词
D O I
10.1038/nature02072
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Peripheral infection is the natural route of transmission in most prion diseases(1). Peripheral prion infection is followed by rapid prion replication in lymphoid organs, neuroinvasion(2) and progressive neurological disease. Both immune cells and nerves are involved in pathogenesis(3,4), 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.
引用
收藏
页码:957 / 962
页数:6
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