Figure 3
Co-infection with a high dose of T. muris does not affect the development of neuropathology at the terminal stage of prion disease. (A) Analysis of T. muris E/S antigen-specific IgG1 (closed circles) and IgG2c (closed squares) levels in the sera of mice 21 d after high dose T. muris infection (~200 infective eggs). Each point represents the mean OD 405 nm ± SEM, n = 3 mice/group. (B) Experiment design. Cartoon shows the relative timings of the oral T. muris infections in relation to the ongoing prion infection in the CNS. Dpi, d post IC prion infection; green arrows, d on which mice were orally infected with a single high dose of T. muris infective eggs. The green triangles represent the relative magnitude of the T. muris-specific immune response, with the peak response occurring by ~21 d and gradually declining afterwards. (C) Mice were injected with ME7 scrapie prions directly into the CNS by IC injection and subsequently orally infected with a high dose of T. muris infective eggs at the times indicated (n = 6 mice/group). Brains were collected from all mice with terminal prion disease and the neuropathology compared. High levels of spongiform pathology (H&E, upper row), heavy accumulations of PrPd (brown, second row), reactive astrocytes (GFAP+ cells, brown, third row) and active microglia (AIF-1+ cells, brown, bottom row) were detected in the brains of all the terminally-affected mice. Haematoxylin was used as a nuclear counterstain (blue). None of the histopathological signs of prion disease were detected in the brains of mice infected with a high dose of T. muris alone. (D) The severity of the spongiform pathology (vacuolation) within each brain was scored on a scale of 1–5 in nine grey matter and three white matter areas as described in the legend to Fig. 1. Each point represents the mean vacuolation score ± SEM, n = 6 mice/group.
