Figure 4. Immunohistochemical expression of the various components of the TGF-β/Smad pathway in the E. multilocularis-infected liver in experimental mice and in AE patients.

A: In experimental mice. Expression of the various components of the TGF-β/Smad pathway at their peak of expression in the liver. TGF-β1: expression at day 90, in most of the immune cells in most of areas with inflammatory granulomas, in the cytoplasm of hepatocytes, endothelial cells of the hepatic sinusoids and fibroblasts; TGF-β RI and RII: expression at day 60, in the cytoplasm of lymphocytes and macrophages in the periparasitic infiltrate and in most of the hepatocytes, fibroblasts, and endothelial cells close to the periparasitic infiltrate; pSmad2/3: expression at day 30, in both the cytoplasm and nuclear of the hepatocytes; Smad4: expression at day 60, in both the cytoplasm and nuclear of the hepatocytes; Smad7: expression at day 90, in the cytoplasm of the hepatocytes. B: In AE patients. Specimen ‘Close’ was taken close to the parasitic lesions (0.5 cm from the macroscopic changes due to the metacestode/granuloma lesion), and Specimen ‘Distant’ was taken in the liver distant from the lesions (the non-diseased lobe of the liver whenever possible, or at least at 10 cm from the lesion). TGF-β1: expressed in most of the immune cells in most of areas with inflammatory granulomas, in the cytoplasm of hepatocytes, endothelial cells of the hepatic sinusoids and fibroblasts; TGF-β RI and RII: expressed in the cytoplasm of lymphocytes and macrophages in the periparasitic infiltrate and in most of the hepatocytes, fibroblasts, and endothelial cells close to the periparasitic infiltrate; pSmad2/3: expressed in both the cytoplasm and nuclear of the hepatocytes; Smad4: expressed in both the cytoplasm and nuclear of the hepatocytes; Smad7: expressed in the cytoplasm of the hepatocytes. The arrowheads indicate the parasitic lesions in the liver of infected mice and human patients. Final magnification: 200×.