Fig. 3: Influx of pro-inflammatory macrophages in BAL.

a Projection of single-cell macrophages/monocytes from −5 dpi (green) and 4 dpi (magenta) 10X BAL samples obtained from three SARS-CoV-2 infected rhesus macaques (Cohort 1) onto the reference UMAP of lung macrophage/monocytes from uninfected rhesus macaques (NCBI GEO: GSE149758³³). b UMAP projections showing the predicted cell type annotations based on the uninfected lung reference split by time of sample collection (Cohort 1). c DotPlots showing the expression of marker genes for the different macrophage/monocyte subsets in SARS-CoV-2 infected BAL samples (Cohort 1). d Log2 fold-changes compared to −5 dpi for APOBEC3A, CHIT1 and MARCO in bulk BAL RNA-Seq data (Cohort 1). Significance was determined using DESeq2. The p values corrected by the default Benjamini and Hochberg method were used *adj p value <0.05, ***adj p value <0.001. The exact p values are included in Supplementary Data 2. Percentage of a given subset out of all macrophage/monocyte subsets at −5 dpi and 4 dpi from all three animals pooled (Cohort 1) (e) and at −7 dpi and 4 dpi from all six animals pooled (Cohort 2) (f). Percentage of a given subset out of all macrophage/monocyte subsets for each animal at −5 dpi and 4 dpi from Cohort 1 (n = 3) (g) and at −7 dpi (n = 5) and 4 dpi (n = 6) for Cohort 2 (h). The black lines indicate the median. p values for Cohort 2 (f) for 4 dpi vs. −7 dpi: CD163+MRC1+ = 0.009, CD163+MRC1+TREM2+ = 0.03, and CD163+MRC1− = 0.004. Contribution of each macrophage/monocyte subset toward the production of the pro-inflammatory genes and ISG—Cohort 1 pooled (i), Cohort 2 pooled (j), Cohort 1 individual (k) and Cohort 2 individual (l). p values for (l): * = 0.03. The percentage contribution was calculated by dividing the sum of normalized expression of a given gene in a macrophage/monocyte subset by the sum of the normalized expression of the gene in all macrophage/monocyte subsets. a–c, e, g, i, k Cohort 1: n = 3 for both −5 dpi and 4 dpi, d Cohort 1: n = 8 for 2 dpi and n = 4 for 4 dpi, f, h, j, l Cohort 2: n = 5 for −7 dpi and n = 6 for 4 dpi. The black lines indicate the median. Statistical analysis was performed using two-tailed Wilcoxon singed rank test for (g, k, l) and two-tailed Mann–Whitney U test for (h) in R v4.2.2. *p value <0.05, **p value <0.01. Source data (d–l) are provided as a Source Data file.