Figure 3
From: M cell-depletion blocks oral prion disease pathogenesis
M cell-depletion blocks prion accumulation in the gut-associated lymphoid tissue (GALT) and spleen. Mice were treated with anti-receptor activator of NF-κB ligand (RANKL) monoclonal antibody (mAb) to deplete their microfold cells (M cells) and orally infected with the ME7 scrapie agent. Tissues were collected 105 days post infection (a and b, n=4 mice per group) or at the end stage of disease (b), n=8 mice per group). (a) High levels of prion protein (PrP)d (brown, right-hand columns) were detected in association with follicular dendritic cells (FDC) (red, left-hand columns) in the B-cell follicles (green, middle columns) of Peyer's patches, mesenteric lymph nodes (MLNs), and spleens of prion-infected control-Ig-treated mice. (b and c) Analysis of adjacent sections by paraffin-embedded tissue-immunoblot analysis confirmed the presence of proteinase K-resistant PrPSc (blue/black). In contrast, no PrPSc was detected in any of the Peyer's patches, MLNs, and spleens of anti-RANKL mAb-treated mice, which lacked M cells at the time of oral exposure. Arrows indicate (a) PrPd and (b) PrPSc accumulation upon the same FDC networks. a, scale bar=100 μm. c, scale bar=200 μm. Clinical observation: presence of clinical signs of prion disease at the time of cull. dpi, days post oral prion infection.
