NR AXRF
AU Levavasseur,E.; Metharom,P.; Dorban,G.; Nakano,H.; Kakiuchi,T.; Carnaud,C.; Sarradin,P.; Aucouturier,P.
TI Scrapie in 'plt' Mice : Role of Dendritic Cell Migration in Prion Pathogenesis
QU International Conference - Prion 2007 (26.-28.9.2007) Edinburgh International Conference Centre, Edinburgh, Scotland, UK - Book of Abstracts: Pathology and Pathogenesis P03.08
IA http://www.prion2007.com/pdf/Prion Book of Abstracts.pdf
PT Konferenz-Poster
AB
Background: During the incubation periods of most peripherally acquired TSEs, increasing amounts of prions accumulate in lymphoid tissues. While precise sites of peripheral accumulation have been described, the mechanisms of prion transport from mucosa and skin to lymphoid and nervous tissues remain unknown. Because of unique functional abilities, dendritic cells (DC) have been suspected to participate in prion pathogenesis.
Aim(s)/Objective(s): Using experimental mouse scrapie models with impaired DC migration, we evaluated the importance of this function in the pathogenesis.
Methods: Scrapie pathogenesis was first studied in normal mice inoculated with live and killed infected DC, and then in mutant (plt) mice with deficient CCL19/CCL21 expression. The plt mutation results in reduced migration of mature DC from the periphery to lymphoid tissues. Groups of mice were infected by intraperitoneal, subcutaneous, intracerebral and oral routes, using different doses of two distinct mouse-adapted scrapie strains (139A and ME7).
Results: In normal mice inoculated subcutaneously with scrapie-infected DC, the incubation was shorter when cells were alive as compared with killed cells. However, early propagation of PrPsc in lymphoid tissues seemed not affected by DC vitality. Mutant plt mice displayed similar infection of secondary lymphoid organs as normal mice, whatever the route of inoculation and scrapie strain. Under certain conditions of transcutaneous inoculation, the incubation and duration of disease were moderately prolonged in plt mice. This was not related to a milder neuropathogenesis, since plt and normal mice were equally susceptible to intracerebral prion challenge.
Conclusion: Our results suggest that DC functions may facilitate prion neuroinvasion. We conclude that peripheral spreading of prions appears poorly dependent on cell migration through the chemokine/receptor system CCL19/CCL21/CCR7, although neuroinvasion might be somehow facilitated by DC.
AD E. Levavasseur, INSERM, France; P. Metharom, C. Carnaud, P. Aucouturier, Université Pierre et Marie Curie and INSERM, France; G. Dorban, Faculty of Medicine, CRPP, Belgium; H. Nakano, NIH, Laboratory of Respiratory Biology, NIEHS, USA; T. Kakiuchi, Toho University School of Medicine, Department of Immunology, Japan; P. Sarradin, INRA, Infectiologie Animale et Santé Publique, France
SP englisch
PO Schottland
EA pdf-Datei und Poster (Postertitel: Scrapie in plt mice: an assessment of the role of dendritic cell migration in TSE)