Fig. 2
Integrative analysis of tissue-level macrophages reveals shared CXCL10+ CCL2+ and FCN1+ inflammatory macrophage states. a Integrative clustering of 74,373 macrophages from individuals from BALF, lung, kidney, colon, ileum, and synovium. b Density plot of cells with non-zero expression of marker genes in UMAP. c Proportion of inflammatory macrophages that express cytokines and inflammatory genes in severe COVID-19 compared to those in inflamed RA, CD, and UC. Orange represents CXCL10+ CCL2+ state-specific genes. d Previously defined inflammatory macrophages from diseased tissues are clustered with the majority of the macrophages from severe COVID-19. e Z-score of the pseudo-bulk expression of marker genes (AUC > 0.6 and Bonferroni-adjusted P < 10−5) for the CXCL10+ CCL2+ and FCN1+ macrophages. Columns show pseudo-bulk expression. f The proportions of CXCL10+ CCL2+ macrophages of total macrophages per donor sample are shown from healthy BALF (n = 3), mild (n = 3), and severe (n = 6) COVID-19, non-inflamed CD (n = 10) and inflamed CD (n = 12), OA (n = 2) and RA (n = 15), and healthy colon (n = 12), non-inflamed UC (n = 18), and inflamed UC (n = 18). Box plots summarize the median, interquartile, and 75% quantile range. P is calculated by Wilcoxon rank-sum test within each tissue. The association of each cluster with severe/inflamed compared to healthy control was tested. 95% CI for the odds ratio (OR) is given. MASC P is calculated using one-sided F tests conducted on nested models with MASC [36]. The clusters above the dashed line (Bonferroni correction) are statistically significant. Clusters that have fewer than 30 cells are removed. g GSEA analysis for each tissue revealed shared enriched pathways for CXCL10+ CCL2+ macrophages: TNF-α signaling via NF-kB (Hallmark gene set), response to interferon gamma (GO:0034341), Covid-19 SARS-CoV-2 infection calu-3 cells (GSE147507 [39]), positive regulation of cytokine production (GO:0001819), response to tumor necrosis factor (GO:0034612), regulation of innate immune response (GO:0045088), and defense response to virus (GO: 0051607)