Fig. 6.

Mtb disease burden upon dual inhibition of HIF-1α and CPT1a in NCoR1^DC−/− mice ex vivo and in vivo

A. Schematic showing the mCherry-Mtb (H37Rv) infection in primary NCoR1^DC−/− BMcDC1s gated on F4/80⁻CD11c⁺CD24⁺ cells with and without combined treatment with KC7F2 and etomoxir. The cells were harvested after 2h and 18h post infection (hpi) and analyzed by flow cytometry.

B. Representative FACS contour plot depicting gating of Mtb infected cells, along with scatter plot and bar graph showing the cumulative percent infection and change in MFI levels with and without combined treatment with KC7F2 and etomoxir at 2h and 18h post infection in NCoR1^DC−/− BMcDC1s. (n = 6)

C. Schematic outline showing the GFP-Mtb (H37Rv) infection in vivo in NCoR1^DC−/− mice with (inhibitors were injected intraperitoneally at day 3, day 8, day 12 and day 16 post infection) and without combined inhibition with KC7F2 and etomoxir. Mice were sacrificed on day 21 to check bacterial burden in CD103⁺ lung DCs (cDC1 counterpart in lungs) and Th cell phenotype in spleen.

D. Scatter plot and bar graph showing the cumulative percent infection and change in Mtb burden (MFI) in lung DCs (gated on CD11c⁺CD103⁺ cells) in NCoR1 DC^−/− mice at day 21 with and without combined treatment with KC7F2 and etomoxir. (n = 8)

E. Representative FACS dot plots depicting the gating of IFN-γ⁺ and T-bet⁺ cells gated on CD3⁺CD4⁺CD44⁺ effector T cells in the Spleen of treated and untreated mice. Scatter plots and bar graphs showed the cumulative percent infection and change in MFI levels at day 21 with and without combined treatment with KC7F2 and etomoxir in NCoR1^DC−/− mice. (n = 5)

*p ≤ 0.05, **p ≤ 0.01, ***p ≤0.001 and ****p ≤0.0001. p-value has been calculated using two tailed unpaired student’s t-test. Error bars represent SEM.