Type I IFN blockade abrogates the inflammatory neutrophil gene signature in TB-susceptible mice and increases expression of genes associated with a T cell response. Bulk RNA-seq was performed on lung tissue from C3HeB/FeJ mice aerosol infected with HN878 while being treated with either anti-IFNAR (αIFNAR, N = 4) or isotype control (N = 3) three times per week from day −1 to day 25, as compared with uninfected mice receiving isotype control antibody (N = 3). (a) Experimental scheme outline. Analysis was performed at the peak of disease at 26 days after infection. (b) All DEGs in either infected group compared with uninfected controls were subjected to k-means clustering. Clusters are annotated based on hallmark genes and pathways. (c) DESeq2-normalized expression values of representative genes from k-means clusters. Data shown represent individual replicate mice as points with lines at the mean. Data are from a single bulk RNA-seq experiment. Statistical analysis: two-way ANOVA with Holm–Sidak post hoc test. Actual adjusted P values are shown or: *, P < 0.05; **, P < 0.01; ***, P < 0.001. See also: Fig. S5, h and i.