Follicular Dendritic Cell-Specific Prion Protein (PrPc) Expression Alone Is Sufficient to Sustain Prion Infection in the Spleen
Figure 9
Effect of FDC-restricted PrPC-ablation on PrPSc accumulation in the brains and spleens of scrapie-affected mice.
Control mice (Prnp+/- mice) and Prnpflox/-→CD21-Cre Prnpflox/- mice that lacked PrPC-expressing FDC were injected i.c. with the scrapie agent directly into the CNS. Brains and spleens were collected from clinically scrapie-affected mice to compare the neuropathology and cellular sites of PrPSc accumulation. A) High levels of spongiform pathology (H&E, upper row), heavy accumulations of PrPd (brown, second row), reactive astrocytes expressing GFAP (brown, third row) and active microglia expressing Iba-1 (brown, bottom row) were detected in the hippocampi of the brains of all clinically scrapie-affected mice. Scale bars, 500 µm. B) High levels of PrPd (red) were detected in association with FDC in spleens from clinically scrapie-affected control mice that contained PrPC-expressing FDC. C) PET blot analysis of analysis of adjacent sections by PET-immunoblot analysis confirmed the presence of PK-resistant PrPSc (blue/black). In contrast, no PrPd or PrPSc was detected in spleens of Prnpflox/-→CD21-Cre Prnpflox/- that lacked PrPC-expressing FDC. Scale bars = 500 µm.