Early accumulation of PrP(Sc) in gut-associated lymphoid and nervous tissues of susceptible sheep from a Romanov flock with natural scrapie.
The immune system is known to be involved in the early phase of scrapie pathogenesis. However, the infection route of naturally occurring scrapie and its spread within the host are not entirely known. In this study, the pathogenesis of scrapie was investigated in sheep of three PrP genotypes, from 2 to 9 months of age, which were born and raised together in a naturally scrapie-affected Romanov flock. The kinetics of PrP(Sc) accumulation in sheep organs were determined by immunohistochemistry. PrP(Sc) was detected only in susceptible VRQ/VRQ sheep, from 2 months of age, with an apparent entry site at the ileal Peyer's patch as well as its draining mesenteric lymph node. At the cellular level, PrP(Sc) deposits were associated with CD68-positive cells of the dome area and B follicles before being detected in follicular dendritic cells. In 3- to 6-month-old sheep, PrP(Sc) was detected in most of the gut-associated lymphoid tissues (GALT) and to a lesser extent in more systemic lymphoid formations such as the spleen or the mediastinal lymph node. All secondary lymphoid organs showed a similar intensity of PrP(Sc)-immunolabelling at 9 months of age. At this time-point, PrP(Sc) was also detected in the autonomic myenteric nervous plexus and in the nucleus parasympathicus nervi X of the brain stem. These data suggest that natural scrapie infection occurs by the oral route via infection of the Peyer's patches followed by replication in the GALT. It may then spread to the central nervous system through the autonomic nervous fibres innervating the digestive tract.
Andréoletti
Olivier
O
UMR INRA-ENVT, Physiopathologie Infectieuse et Parasitaire des Ruminants, Ecole Nationale Vétérinaire de Toulouse, Toulouse, France1.
Berthon
Patricia
P
INRA, Laboratoire de Pathologie Infectieuse et Immunologie, F-37380 Nouzilly, France2.
Marc
Daniel
D
INRA, Laboratoire de Pathologie Infectieuse et Immunologie, F-37380 Nouzilly, France2.
Sarradin
Pierre
P
INRA, Laboratoire de Pathologie Infectieuse et Immunologie, F-37380 Nouzilly, France2.
Grosclaude
Jeanne
J
INRA, Virologie et Immunologie Moléculaires, Jouy-en-Josas, France3.
van Keulen
Lucien
L
Department of Immunology, Pathobiology and Epidemiology, Institute for Animal Science and Health (ID-Lelystad), Lelystad, The Netherlands4.
Schelcher
François
F
UMR INRA-ENVT, Physiopathologie Infectieuse et Parasitaire des Ruminants, Ecole Nationale Vétérinaire de Toulouse, Toulouse, France1.
Elsen
Jean-Michel
JM
INRA, Station d'Amélioration Génétique des Animaux, Auzeville, France5.
Lantier
Frédéric
F
INRA, Laboratoire de Pathologie Infectieuse et Immunologie, F-37380 Nouzilly, France2.
D000375:Aging; D000818:Animals; D004064:Digestive System / Q000276:immunology / Q000378:metabolism*; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005838:Genotype; D007150:Immunohistochemistry; D008221:Lymphoid Tissue / Q000378:metabolism*; D009420:Nervous System / Q000378:metabolism*; D018620:PrPSc Proteins / Q000032:analysis / Q000378:metabolism*; D012608:Scrapie / Q000378:metabolism* / Q000473:pathology; D012756:Sheep / Q000235:genetics / Q000378:metabolism*; D013997:Time Factors
D018620:PrPSc Proteins