Figure 4
From: M cell-depletion blocks oral prion disease pathogenesis
M cell-depletion blocks prion disease susceptibility after oral exposure. Control (control Ig) and M cell-depleted anti-receptor activator of NF-κB ligand (RANKL) monoclonal antibody (mAb)-treated mice were orally infected with ME7 scrapie prions. Brains were collected from clinically scrapie-affected mice and mice that were free of the clinical signs of prion disease at the end of the experiment (454 days after exposure), and the neuropathology within each brain was compared. (a) High levels of spongiform pathology (hematoxylin and eosin (H&E), left-hand column), heavy accumulations of disease-specific prion protein (PrP) (brown, middle column), reactive astrocytes expressing glial fibrillary acidic protein (GFAP) (brown, fourth column), and active microglia expressing Iba-1 (brown, right-hand column) were detected in the brains of all clinically scrapie-affected control mice (upper row). Analysis of adjacent sections by paraffin-embedded tissue-immunoblot analysis confirmed the presence of proteinase K-resistant PrPSc (blue/black, second column). In contrast, none of the M cell-depleted anti-RANKL mAb-treated mice (middle row) developed clinical signs of prion disease during their life spans or displayed histopathological signs of prion disease in their brains. Data are representative of tissues from eight mice per group. (b) Pathological assessment of the spongiform change (vacuolation) in brains from terminally scrapie-affected mice and mice that remained free of the signs of disease at the end of the experiment. Vacuolation was scored on a scale of 0–5 in the following gray (G1–G9) and white (W1–W3) matter areas: G1, dorsal medulla; G2, cerebellar cortex; G3, superior colliculus; G4, hypothalamus; G5, thalamus; G6, hippocampus; G7, septum; G8, retrosplenial and adjacent motor cortex; G9, cingulate and adjacent motor cortex; W1, inferior and middle cerebellar peduncles; W2, decussation of superior cerebellar peduncles; and W3, cerebellar peduncles. Data are representative of tissues from eight mice per group.
