Interaction between dendritic cells and nerve fibres in lymphoid organs after oral scrapie exposure.
In transmissible spongiform encephalopathies (TSEs), the infectious agent, called PrPsc, an abnormal isoform of the cellular prion protein, accumulates and replicates in lymphoid organs before affecting the nervous system. To clarify the cellular requirements for the neuroinvasion of the scrapie agent from the lymphoid organs to the central nervous system, we have studied, by confocal microscopy, the innervations within Peyer's patches, mesenteric lymph nodes and the spleen of mice in physiological conditions and after oral exposure to prion. Contacts between nerve fibres and PrPsc-associated cells, dendritic cells (DCs) and follicular dendritic cells (FDCs), were evaluated in preclinical prion-infected mice. Using a double immunolabelling strategy, we demonstrated the lack of innervation of PrPsc-accumulating cells (FDCs). Contacts between nerve fibers and PrPsc-propagating cells (DCs) were detected in T-cell zones and cell-trafficking areas. This supports, for the first time, the possible implication of dendritic cells in the prion neuroinvasion process.
Dorban
Gauthier
G
Human Histology, Immunology Center, Faculty of Medicine, University of Liège, CHU, Avenue de l'hôpital, Tour de pharmacie +4, 4000 Liège, Belgium. gdorban@ulg.ac.be
Defaweux
Valérie
V
Demonceau
Caroline
C
Flandroy
Sylvain
S
Van Lerberghe
Pierre-Bernard
PB
Falisse-Poirrier
Nandini
N
Piret
Joëlle
J
Heinen
Ernst
E
Antoine
Nadine
N
D000818:Animals; D020566:Dendritic Cells, Follicular / Q000378:metabolism / Q000473:pathology*; D004195:Disease Models, Animal; D007124:Immunoenzyme Techniques; D008198:Lymph Nodes / Q000294:innervation / Q000378:metabolism / Q000473:pathology; D008221:Lymphoid Tissue / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018613:Microscopy, Confocal; D009412:Nerve Fibers / Q000378:metabolism / Q000473:pathology*; D010581:Peyer's Patches / Q000294:innervation / Q000378:metabolism / Q000473:pathology; D018621:PrPC Proteins / Q000378:metabolism; D012608:Scrapie / Q000378:metabolism / Q000473:pathology*; D013154:Spleen / Q000294:innervation / Q000378:metabolism / Q000473:pathology