Fig 5. Role of TNFR-mediated pathways in lipid droplet formation in M. tuberculosis-infected macrophages.

(A) Effect of pathway inhibitors on lipid droplet content of infected macrophages. The scheme at the top of the figure shows the intracellular signaling pathways activated by TNFR1 and TNFR2. Infected MDM were treated either with chemical inhibitors or vehicle; lipid droplet content was measured and results expressed as described in Fig 4. Statistical significance (*p < 0.05) of differences between treated and untreated cells was assessed by one-sample student t-test. Rapamycin: mTORC1 inhibitor, Z-IETD-FMK: caspase 8 inhibitor, Z-DEVD-FMK: caspase 3 inhibitor, QNZ: NF-κB inhibitor, SB203580: p38 inhibitor, JNK-IN-8: JNK inhibitor, GDC-0994: ERK inhibitor. (B) Transcriptomic analysis of human lung tuberculous granulomas. The differential expression between sample classes was determined for 182 Pathway Interaction Database pathways by coincident extreme ranks in numerical observations. 77 pathways were identified at a cutoff false discovery rate of 0.05; the p values for these were plotted onto the x-axis. To represent effect size, pathway gene sets with fewer genes were given greater bar height than were larger sets that yielded similar p values. Four of the pathways discussed in the text are highlighted in orange.