. Do innervation of germinal centre and contacts between FDC and nerve fibers be keys to understand the susceptibility difference between bovines and humans to the BSE agent?

Do contacts between FDC and nerve fibers be keys to understand the

Do contacts between FDC and nerve fibers be keys to understand the

susceptibility difference between

susceptibility difference between

bovines and humans to the BSE agent?

bovines and humans to the BSE agent?

Valérie Defaweux

_{, Gauthier Dorban}

_{, Olivier Jacqmot}

_{, Nadine Antoine}

_{, Ernst Heinen}

3_{Deparment of Morphology and Pathology, Laboratory of Anatomy, Faculty of Medicine Veterinary, University if Liège, Belgium}

Innervation of bovine and human tonsils of calves less than 12 months old/humans less than 5

years (I) and bovine older than 24 months/humans older than 25 years (II)

(I) Human GFAP in green, FDC in red (II) Bovine GFAP in green, FDC in red (II) Human NFL in green FDC in red (II) Bovine NFL in green, FDC in red (II) Human NFH in green FDC in red (II) Bovine NFH in green, FDC in red

.

BSE

vCJD

Prion cell tropism varies significantly among animal

species, depending on both the agent strain and

host-specific factors. 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.

Given that the proximity of mature follicular dendritic

cells (FDC) with nerve endings is known to affect the

speed of prion neuroinvasion and that tonsils are the entry zone for the agent, it appears reasonable to postulate that

mucosal innervation and the interface between nerve fibres and FDC in bovine and human tonsils may

represent one of the host factors influencing the cell tropism and the ways of neuroinvasion of the infectious agent in humans or bovine.

GFAP + fibres

(II) Human

GFAP + fibres

(II) Bovine _{In non-lymphoid compartment, innervation of bovine} and human tonsils is similar. The interfollicular zone,

the connective tissue under the epithelium and the

submucous layer are highly innervated

Sub-epithelial tissue Inter follicular Zone Germinal Centre Bovine tonsils (>24 month old) G F A P + ++ ++ N F -H +/- ++ ++ N F -L +/- ++ ++ Human tonsils (patients >25 years old) G F A P + ++ -N F -H +/- ++ -N F -L +/- ++

-CONCLUSION : The innervation of germinal centre is species dependent

and could be a rate-limiting step to neuroinvasion in humans. This variation could

influence prion lymphotropism and the ways of neuroinvasion and thus explain the

differences of susceptibility of bovine and humans to the BSE agent.