Fig. 4: M. tuberculosis isolate associated with severe TB modulates the macrophage transcriptome.

BMDMs generated from C57BL/6 mice were infected with M. tuberculosis isolates 4I2 or 6C4 at a MOI of 2, or kept non-infected (NI). Six hours post-infection cell cultures were lysed, RNA extracted and subjected to targeted RNA-Seq. a Principal component (PC) analysis for data obtained from M. tuberculosis 4I2-infected (red), M. tuberculosis 6C4-infected (blue) and non-infected (NI, yellow) cells. Venn diagram (b) and volcano plots (c) representing the significantly differentially expressed genes (adjusted p-value ≤ 0.05 and log(fold-change) ≥2 or ≤ –2) when comparing BMDMs infected with M. tuberculosis isolate 4I2 or 6C4 with NI cells. In c, significantly differentially expressed genes (NI versus infected cells; adjusted p-value ≤ 0.05 and log(fold-change) ≥2 or ≤ –2) are shown in orange. Significant genes (adjusted p-value ≤0.05 and log(fold-change) between 2 and –2) are shown in black. Non-significant genes are displayed in light gray. Pathway analysis for significantly expressed genes detected in BMDMs infected with M. tuberculosis isolate 4I2 (d) or 6C4 (e) versus NI cells. Bar plots represent the number of genes present in each identified pathway and the color codes reflect adjusted p-values. In both differential expression analysis and pathway analysis, multiple testing adjustments were performed using the Benjamini–Hochberg (BH) procedure. The 20 most affected pathways are represented for each condition.