Cross-tissue single cell landscape of human monocytes and macrophages in health and disease

Mononuclear phagocytes (MNP) encompass dendritic cells, monocytes and macrophages (MoMac), which exhibit antimicrobial, homeostatic and immunoregulatory functions. We integrated 178,651 MNP from 13 tissues across 41 datasets to generate a MNP single-cell RNA compendium (MNP-VERSE), a publicly available tool to map MNPs and defined conserved gene signatures of MNP populations. Next, we generated a MoMac-focused compendium that revealed an array of specialised cell subsets widely distributed across multiple tissues. Specific pathological forms were expanded in cancer and inflammation. All neoplastic tissues contained conserved tumour-associated macrophage populations. Particularly, we focused on IL4I1+CD274(PD-L1)+IDO1+ macrophages, which accumulated in the tumour periphery in a T cell-dependent manner via IFNg and CD40/CD40L-induced maturation from interferon-primed monocytes. IL4I1_Macs exhibited immune-suppressive characteristics through tryptophan degradation and promoted entry of regulatory T cell into tumours. This integrated analysis provides a robust online-available platform for uniform annotation and dissection of specific macrophage functions in healthy and pathological states. Overall design: Indexed single cell RNAseq (scRNAseq) of human dendritic cells and monocytes from Blood, Liver, Lung, Spleen and Tonsil.