The role of the immune system in TSE agent neuroinvasion

Abstract

Many natural infections with transmissible spongiform encephalopathy (TSE) agents are likely to be acquired peripherally for example, following ingestion of contaminated feed. Following peripheral exposure TSE agents accumulate in lymphoid tissues before spreading to the brain. Many studies have attempted to identify the cells and their components that are required for the delivery of the TSE agent from the site of inoculation to the brain, a process termed neuroinvasion. In the lymphoid tissues of TSE-affected hosts these agents, as identified by disease-specific prion protein accumulations, usually accumulate on follicular dendritic cells (FDCs). Studies of mouse TSE models have shown that mature FDCs are critical for replication of infection in lymphoid tissues and subsequent neuroinvasion. Although examples of FDC-independent neuroinvasion have been described, treatments that interfere with the integrity or function of FDCs reduce TSE susceptibility by blocking the spread of disease to the brain. For example, temporary depletion of FDCs before oral inoculation with TSE agents blocks the accumulation of disease-specific PrP in Peyer’s patches and mesenteric lymph nodes, and prevents neuroinvasion.