Relevance of the regional lymph node in scrapie pathogenesis after peripheral infection of hamsters.
BACKGROUND
The exact role of the lymphoreticular system in the spread of peripheral prion infections to the central nervous system still needs further elucidation. Against this background, the influence of the regional lymph node (Ln. popliteus) on the pathogenesis of scrapie was monitored in a hamster model of prion infection via the footpad.


METHODS
Surgical lymphadenectomy was carried out at different time points after infection, or prior to inoculation, in order to elucidate the impact of the lymph node on lethal neuroinvasion.


RESULTS
The Ln. popliteus did not show an influence on pathogenesis when a high dose of infectivity was administered. However, it was found to modulate the interval of time until the development of terminal scrapie in a subset of animals lymphadenectomized after low-dose infection. In additon, lymphadenectomy performed four weeks before inoculation prevented cerebral PrP(TSE) deposition and development of disease during the period of observation (314 days) in the majority of hamsters challenged with a very low dose of scrapie agent.


CONCLUSIONS
Our findings suggest the regional lymph node as a potentially facilitating or even essential factor for invasion of the brain after peripheral challenge with low doses of infectious scrapie agent. The invasive in vivo approach pursued in this study may be applied also to other animal species for further elucidating the involvement of lymphoid tissue in the pathogenesis of experimental and natural TSEs.
Kratzel
Christine
C
Robert Koch-Institut, P24 - Transmissible Spongiforme Enzephalopathien Nordufer 20, D-Berlin 13353, Germany. chris.kratzel@web.de
Krüger
Dominique
D
Beekes
Michael
M
D000818:Animals; D015153:Blotting, Western; D006224:Cricetinae; D004195:Disease Models, Animal; D005260:Female; D008197:Lymph Node Excision; D008198:Lymph Nodes / Q000378:metabolism / Q000503:physiopathology*; D008297:Male; D008647:Mesocricetus; D018620:PrPSc Proteins / Q000378:metabolism / Q000472:pathogenicity*; D012608:Scrapie / Q000503:physiopathology*
D018620:PrPSc Proteins