Pr

1
Do contacts between FDC and nerve fibers be keys
to understand the susceptibility difference
between bovines and humans to the BSE agent?
Valérie Defaweux1, Gauthier Dorban1, Olivier
Jacqmot3, Nadine Antoine2, Ernst
Heinen1 1Department of Morphology and Immunology,
Institute of Human Histology, Faculty of
Medecine, University of Liège, Belgium 2Department
of Morphology and Pathology, Laboratory of
Animal Histology, Faculty of Medicine Veterinary,
University of Liège, Belgium 3Deparment of
Morphology and Pathology, Laboratory of Anatomy,
Faculty of Medicine Veterinary, University if
Liège, Belgium
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.
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)
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 (gt24 month old) GFAP
Bovine tonsils (gt24 month old) NF-H /-
Bovine tonsils (gt24 month old) NF-L /-
Human tonsils (patients gt25 years old) GFAP -
Human tonsils (patients gt25 years old) NF-H /- -
Human tonsils (patients gt25 years old) NF-L /- -
(I) Human
(II) Human
(II) Human
NFH in green FDC in red
GFAP in green, FDC in red
NFL in green FDC in red
(II) Bovine
(II) Bovine
(II) Bovine
NFH in green, FDC in red
GFAP in green, FDC in red
NFL in green, FDC in red
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.