SPP1 ⁺ macrophage interaction with fibroblasts in TB. (A) Circos plot showing proportion of inferred signals upregulated in TB-diseased lungs from LIANA analysis with fibroblasts as sender and macrophage subclusters as receivers. (B) LIANA analysis on detailed cell level with SPP1⁺ macrophage as sender. Circos plot showing proportion of inferred signals upregulated in TB-diseased lungs sending from SPP1⁺ macrophage to broad cell groups, with fibroblasts at the top. (C) Evaluation of markers gene expression for SPP1⁺ TAM from PDAC by Raghavan et al. (2021) on macrophage subclusters in this study. (D) Evaluation of marker gene expression for monocyte-derived macrophage (MDM) subsets from the HLCA on macrophage subclusters in this study. (E) Specific upregulated ligand–receptor pairs and involved receiver cells in the LIANA analysis with SPP1⁺ macrophage as sender. (F) Left: Fluorescence immunohistochemistry staining images of human lung granuloma with DAPI (nuclear), SPP1 (SPP1⁺ macrophage), CD68 (pan macrophage marker), and CD206 (macrophage enriched in alveolar spaces). Scale bars: 1 mm. Middle: Quantified SPP1 expression from 10 ROIs (5 μm/pixel) in outer cellular layer, inner cellular layer, or the necrotic core of the granulomas. Right: Expression ratio of SPP1 and CD68 between inner cellular layer and outer layer and inner cellular layer and necrotic core. The images in F come from serial sections of the same TB granuloma depicted by Mpotje et al. (2025), Preprint. As both studies identify macrophages, the macrophage stain CD68 is shown in both. However, this current study colocalizes with CD206 and SPP1, while the preprint co-stains with ALOX5. Two-sided Mann–Whitney U test without correction was used on each module. Statistical annotations: P value < 0.001 (***); P value > 0.05 (ns).