Fig. 2: GM-CSF controls transcriptional signatures associated with TB pathogenesis.

WT mice were infected and/or treated as in Fig. 1a. Blood and lungs were collected from M. tuberculosis HN878-infected and uninfected mice for RNA-Seq analysis (n = 4–5 mice/group). a Blood modules of co-expressed genes derived using WGCNA from human TB datasets³⁵ are shown for blood RNA-Seq datasets obtained from infected mice treated with αGM-CSF or Ctrl mAbs, compared to uninfected Ctrl Ab treated mice (Supplementary Data 3). c Lung modules of co-expressed genes derived using WGCNA from mouse lung disease modules³⁶ are shown for lung RNA-Seq datasets obtained from infected mice treated with αGM-CSF or Ctrl mAbs, compared to uninfected Ctrl Ab treated mice (Supplementary Data 5). a, c Fold enrichment scores derived using QuSAGE are depicted, with red and blue indicating modules over- or under-abundant, compared to the controls. Colour intensity and size of the dots represents the degree of perturbation, indicated by the colour scale, with the largest dot representing the highest degree of perturbation within the plot. Only modules with fold enrichment scores with FDR P-value < 0.05 were considered significant and depicted here. Module name indicates biological processes associated with the genes within the module. b, d Boxplots depicting the module eigengene expression, i.e., the first principal component for all genes within the module, are shown for uninfected Ctrl Ab (light green) or αGM-CSF (light purple) and infected Ctrl Ab (dark green) or αGM-CSF (dark purple) treated groups (n = 4–5 mice/group), for (b) blood modules: Inflammasome/Granulocyte (HB3), Innate/hemopoietic mediators (HB5), Innate Immunity/PRR/C’/Granulocyte (HB8), Interferon/PRR (HB12) and Interferon/C’/Myeloid (HB23); and (d) lung modules: Type I IFN/Ifit/Oas (L5), Myeloid/granulocyte function (L10), IL-17 pathway/granulocytes (L11), Inflammation/IL-1 signalling/myeloid cells (L12), and Myeloid cells/Il1b/Tnf (L13). Gene expression profiles are shown using boxplots, where the upper and lower box limits show the interquartile range (limits of second and third quartiles), a thick horizontal bar within the box shows the median, whiskers show the minimum and maximum values, and each dot represents an individual mouse (n = 4–5 mice/group). C’, complement.; PRR, pathogen recognition receptor. GCC, glucocorticoid; K-channel, potassium channel; TM, transmembrane; Ubiq, ubiquitination.