Distribution of nerve fibres in bovine and human mucosal associated lymphoid tissues

Prion cell tropism varies significantly among animal species, depending on both the agent strain and host-specific factors. For example, prions show high lymphotropism in scrapie infected sheep and vCJD, but little, if any, in sCJD or BSE. In particular, the BSE strain is associated with significant PrP-res accumulation in tonsils, spleen and appendix in humans, whereas it is largely confined to the nervous system in infected cattle. Therefore, at least in the case of BSE and vCJD, it appears that host properties can influence the accumulation of the infectious agent in lymphoid organs. Mature FDC play an important role in prion pathogenesis, since neuroinvasion following peripheral challenge is significantly impaired in their absence. The proximity between these FDC and sympathetic nerve endings is known to affect the speed of prion neuroinvasion.

In this study, we analysed the mucosal innervation and the interface between nerve fibres and FDC in bovine and human tonsils and in ileal and jejunal bovine Peyer’s patches using a panel of antibodies observed by confocal microscopy. Since differences in the innervation of lymphoid organs depending on age have been reported, we analysed three categories of bovine ages (new born calves, calves less than 12 months old and bovines older than 24 months) and two categories of human ages (patients less than 5 years old and patients older than 25 years).

In both species, hypothetical ways of innervation by-passing germinal centre could be postulated: nerve fibres are widely distributed in antigens/cells traffic area (the lamina propria, the interfollicular zone, the suprafollicular dome in Peyer’s patches and the lymphoepithelial area in tonsils). We pointed out that, only in ileal and jejunal Peyer’s patches and in tonsils of bovines older than 24 months, nerve fibres are observed to be in contact with FDC. In contrast, in human tonsils, no nerve fibres established contact with FDC, whatever the age. Thus, innervation of germinal centres can be said to be an age-dependent dynamic process in bovines and a weak innervation of the secondary lymphoid organs could thus be a rate-limiting step to neuroinvasion in humans. This variation could influence the way of neuroinvasion and thus, the differences of susceptibility of bovines and humans to the BSE agent.