From: TSS ()
Subject: Relevance of the regional lymph node in scrapie pathogenesis after peripheral infection of hamsters
Date: September 25, 2007 at 8:32 am PST
Relevance of the regional lymph node in scrapie pathogenesis after peripheral infection of hamsters
Christine Kratzel , Dominique Kruger and Michael Beekes
BMC Veterinary Research 2007, 3:22doi:10.1186/1746-6148-3-22
Published: 25 September 2007
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.
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.
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 PrPTSE 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.
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.
Taken together, our interventional study did not show any discernible
pathogenetic influence of the regional lymph node on preventing or mediating
neuroinvasion of scrapie agent when a relatively high dose (2%, 1%, or 0.1%
inoculum) of scrapie agent was administered prior to, or after lymphadenectomy.
Indeed, recent studies using the same hamster model and similar doses of agent
revealed the regional nerve (N. ischiadicus) as the prime pathway for CNS
invasion of the scrapie agent after footpad-infection, as evidenced by a substantial
prolongation of survival after neurectomy (Kratzel et al., submitted for
However, findings from our first experimental series reported here indicated that
the Ln. popliteus may have modulated the incubation time in a limited subset of
animals upon low dose infection with the 0.01% inoculum when
lymphadenectomy was performed at different time points after footpad-infection.
In these experiments, our findings suggested the regional lymph node as a
potentially facilitating factor contributing to neuroinvasion. This conclusion was
confirmed and expanded by the results of our second set of experiments, when a
very low dose of agent (0.001% inoculum) was administered to hamsters that
were lymphadenectomized four weeks before infection: Under these conditions
lymphadenectomy prevented detectable cerebral prion invasion - as monitored by
PET blotting – in a large proportion of animals (table 2 and figure 3).
It has been well established that the lymphoid pathogenesis of acquired TSEs
depends on a variety of parameters such as the host species, the strain and dose of
agent, or the route of infection . Contrary effects of splenectomy have been
observed in mice and hamsters [18, 34], and Glaysher and Mabbott  reported
impaired neuroinvasion after scrapie infection via the skin of genetically modified
mice lacking draining lymph nodes. We suggest the application of our invasive in
vivo model in mice and other animal species to further elucidate the involvement
of lymphoid tissue in the pathogenesis of experimental and natural TSEs.
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