Interaction between dendritic cells and nerve fibres in lymphoid organs after oral scrapie exposure

Abstract

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.

Spreading of prions from the immune to the peripheral nervous system: a potential implication of dendritic cells

“…10). The absence of a negative eVect of prions upon the neurites network is in accordance with in situ observations made on diVerent species (Dorban et al 2007a;Marruchella et al 2009). …”

“…An up-todate in vitro study has shown that infected dendritic cells are able to transmit prions to primary neurons from the CNS by the intermediary of tunneling nanotubes (TNT) (Gousset et al 2009). Previously we have also demonstrated that CD11c-DCs established a lot of contacts with the nerve Wbers inside the mouse Peyer's patches in physiological conditions and following a scrapie challenge (Defaweux et al 2005;Dorban et al 2007a). Similar results have been obtained within sheep Peyer's patches (Marruchella et al 2007;Chiocchetti et al 2008).…”

“…The hypothesis of the implication of DCs-peripheral nerve Wbers interfaces in the pathogenesis of prion diseases originally resulted from in vivo studies that described neuroimmune connections in scrapie-infected lymphoid organs (Defaweux et al 2005;Ma et al 2007;Dorban et al 2007a). In contrast to other models based on neuroblastoma Fig.…”

Neural networks in intestinal immunoregulation

“…The presence of noradrenergic fibers was reported in PPs implying that the sympathetic nerve could play a role in the regulation of the immune response. Noradrenergic axonal fibers are found in close proximity to DCs, 11 plasma cells and in T cell zones 12 . NA can affect DCs migration as well as their cytokine production (i.e., IL12, IL-6 13 ) through the binding to adrenoceptors (β2 13 , α1, 14 α2 15 , 16 ).…”

Orally Administered Prion Protein Is Incorporated by M Cells and Spreads into Lymphoid Tissues with Macrophages in Prion Protein Knockout Mice

“…51 These contacts in the peripheral lymph nodes and spleen are assumed to be important for neuroinvasion of the infectious agent. 52,53 Therefore, these findings suggest the possibility that PrP-positive macrophages in Peyer's patches and the spleen may be involved in neuroinvasion, and neuroinvasion can occur a few hours after an oral infection.…”