Indoleamine 2,3-dioxygenase 1 (IDO1) activity arrests the apoptosis of Mycobacterium tuberculosis (M. tuberculosis)-infected macrophages

<b>Introduction:</b> M. tuberculosis is phagocytosed and can persist and survive inside macrophages. It is not clear why these infected macrophages do not become apoptotic. IDO1 is expressed abundantly in tuberculoid granuloma and catabolizes tryptophan, which impairs growth of intracellular M. tuberculosis. However, M. tuberculosis can synthesis tryptophan independently and thus may compensate the effect of IDO1. We hypothesized that the IDO1 activity prevents M. tuberculosis-infected macrophages from going into apoptosis. <b>Method:</b> THP-1 cells were differentiated to macrophages with PMA and infected with mc2 6030 (not translocating to cytoplasm) and mc2 6020 (translocating to cytoplasm), after which IDO1 was induced by interferon gamma (IFNg). IDO1 activity was inhibited by either 1-Methyl-D-tryptophan (1-D-MT) or BMS-986205. The IDO1 activity were determined by metabolites of tryptophan using UPLC/tandem mass spectrometry. Flow cytometry was used to measure percentage of apoptotic cells in samples of THP1 macrophages stained with the Alexa FluorR 488 Annexin V/Dead Cell Apoptosis Kit. <b>Result:</b> Apoptosis frequencies increased treated with both IDO1 inhibitors (1-D-MT and BMS-986205) and decreased when treated with IFNg. Interestingly, there was a strain dependency. The preliminary findings indicate that IDO1 attenuate apoptosis significantly at 120 h when infected macrophage with mc2 6030 M. tuberculosis. <b>Conclusion:</b> We conclude that IDO1 activity may arrest apoptosis of M. tuberculosis-infected macrophages. This suggests IDO1 activity may be a therapeutic target and can be manipulated for the clearance of M. tuberculosis.