Figure 4: Macrophage activation phenotypes in mice and humans under homoeostatic and disease conditions. | Nature Communications

Figure 4: Macrophage activation phenotypes in mice and humans under homoeostatic and disease conditions.

From: Natural variation of macrophage activation as disease-relevant phenotype predictive of inflammation and cancer survival

Figure 4

(a) Homoeostatic tissue-resident macrophage populations of C57BL/6J mice were compared in their expression of the M(LPS)+ and M(LPS)− signature using GSEA. Bone-marrow derived macrophages (BMDM)+LPS served as M1-skewed control. All data from the Immgen project (GSE15907 with n= 2–3 averaged per cell type) and BMDM+LPS from GSM1151665. (b) Classification of tissue-resident macrophages (C57BL/6J mice) in the M(LPS)+/− activation axis by dividing the GSEA normalized enrichment score (NES) for M(LPS)+ and M(LPS)− genes for each data set. Numbers greater or smaller than 0 indicate high and low LPS responsiveness, respectively. BMDM-M-CSF from GSM1150712. Source of other data indicated in a. (c) GSEA of M(LPS)+/− signatures (top 200 genes) in human alveolar macrophages obtained by bronchoscopic lavage before (bottom panel) and after LPS (top panel) instillation. All genes of the control and LPS data set are ranked by differential expression. Vertical lines indicate a match of genes with the respective signature. Data from GSE40885. (d) Human isolated peripheral blood mononuclear cells (PBMC) were sequenced from patients presenting with systemic inflammatory response syndrome (SIRS) and sepsis at day 1 (d1) and 3 (d3) after clinical diagnosis. The transcriptome was analysed for enrichment of M(LPS)+ genes in differentially expressed genes (disease versus healthy control) using GSEA. Data from GSE13904. (e) GSEA of M(LPS)+ signature genes in isolated human synovial CD14+ macrophages from healthy (n=3) and rheumatoid arthritis (RA) patients (n=5). The top 25 leading edge genes are shown as heatmap (red=upregulated, blue=downregulated). Data from GSE10500. (f) GSEA of M(LPS)+ signature genes in laser-dissected glomerula from healthy controls (n=14) and patients with lupus nephritis (n=32). The top 25 leading edge genes are shown as heatmap for four controls and four lupus patients (red=upregulated, blue=downregulated). Data from GSE32591.

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