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Immunological and structural studies of prion diversity

Final Report Summary - IMMUNOPRION (Immunological and structural studies of prion diversity)

IMMUNOPRION was a project at the cutting-edge of current scientific knowledge on Transmissible spongiform encephalopathies (TSEs). The project was built around three key issues: the strain diversity of TSE agents; the crossing of the species barrier; and the evaluation of the host innate and acquired immune responses. TSEs are diseases that affect the brain and the nervous system of humans and animals, among which we find what is commonly termed mad cow disease and its human equivalent, Creutzfeldt-Jakob disease (vCJD). TSEs are propagated by prions (a type of infectious agent made exclusively of protein) through the food chain.

IMMUNOPRION investigated the fundamental features of TSEs to develop the detection of prion strains for diagnostic procedures and for the control of their dissemination through the food chain. The project's objectives were organised around the idea that a rational food safety strategy must prevent, predict and protect.

The project evaluated the effect of DSS inoculation on sympathetic innervation of the colon, and showed a decrease of sympathetic innervation and that Dendritic cells (DC) were less in contact with nerve fibres than in control mice. These data are correlated with a reduction of the neuro-immune interfaces. Gut inflammation by DSS appears to block prion progression probably as a result of a loss of terminal endings. This observation is consistent with other work and supports the idea that the fate of the disease is determined during the early days which follow oral infection. Experiments in rats offer the possibility to recover immune cells by in vivo cannulation of the nodes. Intestinal inflammation led to accumulation of macrophages and peripheral monocytes in the mesenteric lymph nodes which can be further examined for their PrPsc contents.

In conclusion, altogether these works strengthen the evidences that the immune system plays a crucial role in the barrier species in providing new insights and innovative tools to further study the mechanisms of the transmission of prions.