Systems biology predicts that fibrosis in tuberculous granulomas may arise through macrophage-to-myofibroblast transformation
Fig 7
Characterization of fibrosis in the granuloma.
A-D: IHC stains for α SMA (left panels) and corresponding Geographically Information System (GIS) analysis-identified locations of fibroblasts (right panels) for four unique non-human primate granulomas. Objects identified as fibroblasts are highlighted in cyan, and the granuloma boundary demonstrated by the solid yellow line. E, F: Distribution of lengths (E) and widths (F) of αSMA+ cells for each granuloma respectively. G: Total numbers of αSMA+ cells for each granuloma, respectively. Cells with length or width of greater than three standard deviations away from the mean size were classified as outliers and removed from the plots in E-G.H-J: Representative IHC staining of fibrotic granuloma demonstrate that αSMA (green) expressing cells in the fibrotic cuff co-express CD11c (red), vimentin (blue), and CD31 (cyan). H: Expected expression levels of markers shown in panel I for each cell type involved in fibrosis. Colors correspond to the stains used in B and semi-opaque represents low expression. I: Full staining on sample C. J: Inset, αSMA, vimentin, CD11c, CD31 (left to right).