Experimental scraple in 'plt' mice:: an assessment of the role of dendritic-cell migration in the pathogenesis of prion diseases

被引:17
作者
Levavasseur, Etienne
Metharom, Pat
Dorban, Gauthier
Nakano, Hideki
Kakiuchi, Terutaka
Carnaud, Claude
Sarradin, Pierre
Aucouturier, Pierre [1 ]
机构
[1] Univ Paris 06, UMR S 712, Paris, France
[2] Hop St Antoine, INSERM, UMR S 712, F-75012 Paris, France
[3] Univ Liege, Fac Med, CRPP, B-4020 Liege, Belgium
[4] NIEHS, Lab Resp Biol, NIH, Res Triangle Pk, NC 27709 USA
[5] Toho Univ, Sch Med, Dept Immunol, Tokyo, Japan
[6] IASP, UR1282, INRA, F-37380 Nouzilly, France
关键词
D O I
10.1099/vir.0.82816-0
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 ; 0836 ; 090102 ; 100705 ;
摘要
Peripherally acquired transmissible spongiform encephalopathies display strikingly long incubation periods, during which increasing amounts of prions can be detected 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 (DCs) have been suspected to participate in prion pathogenesis. In mice inoculated subcutaneously with scrapie-infected DCs, the incubation was shorter when cells were alive as compared with killed cells, suggesting that DC functions may facilitate prion neuroinvasion. However, early propagation in lymphoid tissues seemed not importantly affected by DC vitality. Mutant (plt) mice that have deficient CCL19/CCL21 expression and DC migration displayed similar infection of secondary lymphoid organs as normal mice, regardless of 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. We conclude that peripheral spreading of prions appears poorly dependent on cell migration through the chemokine/receptor system CCL19/CCL21 /CCR7, although DCs might be able to help prions reach sites of neuroinvasion.
引用
收藏
页码:2353 / 2360
页数:8
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