Increased M. tuberculosis load and earlier immune response in C57BL/6 as compared with TB-susceptible C3HeB/FeJ-infected mice. (a and b) C57BL/6 and C3HeB/FeJ mice were aerosol infected with the indicated M. tuberculosis strains, and M. tuberculosis CFUs in lung tissue were determined at the indicated time points. Data in a and b are from single experiments with N = 5 mice per group and are representative of a minimum of two independent experiments. Statistical analysis: (a) two-way ANOVA with Holm–Sidak post hoc test; (b) unpaired t test for HN878 and 6C4, unpaired t test with Welch’s correction for 4I2; *, P < 0.05; ***, P < 0.001; ****, P < 0.0001. (c–f) Bulk RNA-seq was performed on whole lung tissue and whole BAL cell pellets from mice infected with HN878 at the indicated time points, as compared with uninfected controls. (c and e) Principal component analysis of all protein-coding, immunoglobulin, and T cell–receptor genes in bulk RNA-seq data from whole lung tissue and whole BAL cell pellets. (d and f) All DEGs in whole lung and BAL at any time point compared with the respective uninfected controls were subjected to k-means clustering. Clusters are annotated based on representative hallmark genes and pathways. Data in c–f are from a single bulk RNA-seq experiment with N = 5 mice per group. See also Fig. S1, a and b.