Fig. 5. IFN-γ mediated control of HAL and HDC up-regulation.

a A 10-fold decrease in bacillary counts for ΔhisD compared to that of H37Rv and chisD was detected in infected B6 mice lungs on day 28. In B6 IFN-γ^−/− mice however, ΔhisD, chisD and H37Rv exhibit near identical bacillary counts on day 28 (n = 6 individual mice per time point; mean and SEM; *P-value < 0.05, **P-value < 0.005). b A similar extent of lung damage was observed in B6 IFN-γ^−/− mice infected with H37Rv, ΔhisD and chisD on day 28 (pictures are representative of six individual mice lungs samples). c Negligible expression of host histidine sequestering enzymes and Mtb histidine biosynthesis enzymes in the whole lung lysates from B6 IFN-γ^−/− mice infected with H37Rv. Mice β-Actin serves as the loading control. (Immunoblots are representative of samples obtained from three mice each time point). d Addition of specific inhibitors of HAL and HDC ΔhisD-infected primary macrophages significantly reverses the bactericidal effects of CD4 T cell activation, 48 h post infection (n = 5 independently acquired and cultured primary cells; mean and SEM; **P-value < 0.005).