Assessing the involvement of migratory dendritic cells in the transfer of the scrapie agent from the immune to peripheral nervous systems

Many transmissible spongiform encephalopathy (TSE) agents accumulate upon follicular dendritic cells (FDCs) in lymphoid tissues before spreading to the brain. How TSE agents spread from FDCs to the nervous system is not known as there is no physical FDC-nerve synapse. As FDCs form immobile networks we investigated whether other mobile cells might transfer TSE agents between FDCs and peripheral nerves. We show that scrapie-infected mononuclear cells, B cells and migratory dendritic cells (DCs) were unable to efficiently transmit disease to the peripheral nervous systems (PNSs) of FDC-deficient TNFR1(-/-) mice. These findings differed significantly from a similar study which suggested that scrapie-infected DCs could efficiently transmit disease directly to FDC-deficient RAG1(-/-) mice. Comparison of the innervation in spleens from TNFR1(-/-) mice and RAG1(-/-) mice indicated that the density of sympathetic nerves was much higher in RAG1(-/-) mice. These data imply that DCs could efficiently transmit disease directly to RAG1(-/-) mice because their spleens were highly innervated, but not to TNFR1(-/-) mice because their spleens were less densely innervated. As the density of the innervation in the spleens of wild-type mice also appeared to be much lower than that of RAG1(-/-) mice our data suggest that DCs are unlikely to play a key role in the transfer of TSE agents from FDCs to the PNS of wild-type mice.