Figure 7

Relative IDO-1 activity helps dictate the level of protection by TB granulomas. IDO-1 activity can also be an indicator of the protectiveness of a granuloma. When there is an optimal level of IDO-1 inhibition, the remodeling of the granulomas allows access of CD4⁺ T cells to the central core of the granuloma, resulting in Mtb death. However, excessive or insufficient IDO-1 activity leads to an unprotective granuloma. An excess of IDO activity results in an unprotective, hypoinflammatory granuloma, characterized by deficient proliferation of CD4⁺ and CD8⁺ T cells and poor access of CD4⁺ T cells to the granuloma core, allowing Mtb to grow within the center. On the other hand, an insufficient level of IDO-1 activity leads to an unprotective, hyperinflammatory granuloma, characterized by excess IL-17 production and excess neutrophil influx and granuloma necrosis. IDO-1 is also responsible for the catabolization of tryptophan (a molecule necessary for Mtb growth) into kynurenine. A deficiency of IDO-1 would in turn increase levels of tryptophan and allow for more Mtb growth. IDO-1, indoleamine 2,3-dioxygenase; IL-17, interleukin-17; Mtb, Mycobacterium tuberculosis;.