Fig. 4: Single-cell RNA-seq identifies a positive feedback loop between IFNγ-producing T cells and SARS-CoV-2-infected alveolar macrophages.
From: Circuits between infected macrophages and T cells in SARS-CoV-2 pneumonia
a, UMAP plot showing integrated analysis of 77,146 cells isolated from 10 patients with severe COVID-19 within 48 h after intubation. DC1, conventional dendritic cells type 1 (CLEC9A+); DC2, conventional dendritic cells type 2 (CD1C+); migratory DC, migratory dendritic cells (CCR7+); pDC, plasmacytoid dendritic cells (CLEC4C+); mixed myeloid, mixed cluster containing transitory dendritic cells and very immature monocyte-derived macrophages; iNKT cells, invariant natural killer T cells; Treg, regulatory T cells (FOXP3+). b, Heat map demonstrating expression of the selected genes of interest in two subsets of tissue-resident (TRAM1 and TRAM2) and four subsets of monocyte-derived (MoAM1, MoAM2, MoAM3 and MoAM4) alveolar macrophages. Each column represents a single patient with COVID-19. The MRC1 gene encodes CD206. c, Expression of IFNG is restricted to T cells. d, Detection of SARS-CoV-2 transcripts. Plot shows cumulative number of SARS-CoV-2 genes plus negative strand. e–g, Specific upregulation of CXCL10 (e), CCL4 (f) and IL1B (g) in TRAM2 cells. Density projection plots, expression averaged within hexagonal areas on UMAP. h, Heat map demonstrating selected differentially expressed genes between two subsets of tissue-resident alveolar macrophages (TRAM1 and TRAM2). i, SARS-CoV-2 infection is spatially restricted. Combined immunofluorescence microscopy for CD206, a marker of mature macrophages (red arrows) and smFISH (RNAscope) for positive- (yellow arrowheads) and negative-strand (cyan doublehead arrows) SARS-CoV-2 transcripts. Expanded regions show infected and non-infected CD206-positive alveolar macrophages in the adjacent alveoli.
