Mycobacterium tuberculosis subverts negative regulatory pathways in human macrophages to drive immunopathology
Fig 3
PI3Kδ expression is suppressed in human TB granulomas and infected macrophages.
A, B. Immunohistochemistry analysis of normal human lung tissue demonstrates that alveolar macrophages express both CD68 and PI3Kδ. C, D. Within human lung TB granulomas, CD68 is widely expressed, but no PI3Kδ immunoreactivity is observed. E, F. Both epithelioid macrophages and multinucleate giant cells around TB granulomas express CD68, but neither express PI3Kδ. G. In primary macrophages, Mtb infection significantly upregulates MMP-1 expression at 24h, whilst (H) concurrently suppresses PIK3CD mRNA accumulation. Immunohistochemistry images are representative of six donors with histopathologically confirmed TB who had lung biopsies as part of their routine clinical care. Scale bars: A, B, E, F: 100μm, C, D: 500 μm. Cellular experiments were performed in triplicate and are representative of at least three donors. P values are t-test comparisons.