PrP^c overexpression by the hematopoietic cells favors prion agent replication in the spleen of reconstituted Prp^0/0 mice.

<p>Spleen of Prp^0/0 mice lethally irradiated reconstituted with femoral bone marrow cells from Tga20 (inverse triangle) or B6 (circle) mice and inoculated with RML (black) or ME-7 (grey) strains were sampled 450 days post-inoculation and subsequently inoculated to Tga20 mice. Days post-inoculation (DPI) are represented. A <i>P</i> value of 0.001 was obtained using the Mann-Whitney t-test when comparing the Tga20→Prp^0/0 and B6→Prp^0/0 mice.</p

No difference in disease incubation period is observed in Tga20 chimeric mice inoculated with limiting doses of the RML strain (10⁻⁷ LogLD50).

<p>Tga20 mice were lethally irradiated, reconstituted with femoral bone marrow cells from B6 (square), Tga20 (triangle) or Prp^0/0 (circle) mice and inoculated with the RML prion scrapie strains. The incubation periods are expressed as days post-inoculation (DPI). At this low dose, only 7/10 mice developed scrapie. A <i>P</i> value of 0.19 was obtained using the Kruskal-Wallis ANOVA test when comparing the three groups of mice.</p

Routes of prion neuroinvasion after peripheral exposure.

<p>(a) Natural prion diseases are often acquired <i>via</i> peripheral exposure such as orally, or through skin lesions. How prion reaches its peripheral targets is not known. (b) Direct invasion of the central nervous system might occur with high doses of prion or exposure to neuroinvasive strains. (c) Whereas after exposure to limiting doses of infectivity or less neuroinvasive strains, replication in FDCs in the germinal centers of local lymphoid tissues might be necessary prior to neuroinvasion via closely associated nerve fibers. FDCs are dependent on the presence of B lymphocytes for maturation signals, such as lymphotoxin. (d) Haematogenous spread of infectivity <i>via</i> circulating bone marrow derived cells would not play a role in direct neuroinvasion.</p