Figure 5.

Nutritional immunity to Mtb. (A) Depletion of tricarboxylic acid (TCA) cycle and potential glyoxylate shunt substrates via a cis-aconitate decarboxylase known as immunoresponsive gene-1 (IRG1) that resides in mitochondria. Position at which IRG1 blocks anaplerotic substrate production for Mtb is shown. Isocitrate lyases 1 and 2 (ICL1/2) that serve as important Mtb anaplerotic enzymes in the glycoxylate shunt and that are the functional Mtb paralogs of methylcitrate lyases (MCLs) in the methylcitrate pathway (Muñoz-Elias et al. 2006) are also depicted. (Adapted from data in Michelucci et al. 2013.) (B) Tryptophan depletion by the IFN-γ-induced enzyme, indolamine-2,3-dioxygenase (IDO), in activated macrophages. Mtb genes encoding the enzymes known to be involved in generating precursors of tryptophan biosynthesis are shown in blue font.