scRNA-seq reveals earlier increases in monocyte-derived cell and effector CD4 ⁺ T cell subsets in relatively TB-resistant C57BL/6 mice. C57BL/6 and C3HeB/FeJ mice were aerosol infected with M. tuberculosis HN878 and lung CD45⁺ leukocytes enriched at 14 and 20 days after infection, as well as from uninfected controls, fixed, cryo-preserved, and subsequently pooled for scRNA-seq. (a) UMAP of integrated and clustered data from all experimental groups (N = 3 per group); cDC, conventional dendritic cell; pDC, plasmacytoid dendritic cell. (b) Dot plots showing relative expression of selected marker genes in two neutrophil scRNA-seq clusters. Circle sizes represent the abundance of cells expressing the marker gene, as a percentage of all cells in the cluster within all samples in the analysis. Circle color is proportional to the mean expression of the gene within all cells in the cluster. (c and d) Differential abundance analysis of (c) myeloid cell clusters and (d) T and NK cell clusters in the different conditions in C57BL/6 and C3HeB/FeJ mice, compared with their respective uninfected controls, as determined by Dirichlet-multinomial regression. *, P < 0.05; **, P < 0.001. Points show individual replicate mice with bars at the mean ± standard error. Data shown are from a single scRNA-seq experiment with N = 3 mice per group. See also Fig. S1, j–n.