IDO-Mediated Immune and Metabolic Dysregulation in Schwann Cells Exposed to Mycobacterium leprae

Leprosy is a chronic infectious disease that targets the peripheral nervous system, leading to peripheral neuropathy. <i>Mycobacterium leprae</i> primarily infects Schwann cells, adipocytes, and macrophages, altering their metabolism and gene expression. This study investigates the metabolic interaction between <i>M. leprae</i> and Schwann cells, with a focus on indoleamine 2,3-dioxygenase (IDO), a key enzyme in tryptophan catabolism via the kynurenine pathway. We found that <i>M. leprae</i> induces IDO expression in Schwann cells, suggesting a role in immune modulation and neuropathy. Inhibition of IDO with 1-methyl-L-tryptophan (1-MT) reduced Schwann cell viability and metabolic activity in response to <i>M. leprae</i>. After 24 h of infection, <i>M. leprae</i> impaired mitochondrial membrane potential, although no significant changes in autophagy or mitochondrial ultrastructure were observed by electron microscopy. Interestingly, IDO1 inhibition upregulated the expression of antioxidant genes, including <i>GPX4</i>, <i>NFE2L2</i>, and <i>HMOX1</i>. In conclusion, these findings highlight a central role for IDO in shaping the metabolic and immunological response of Schwann cells to <i>M. leprae</i> infection. IDO induction contributes to immune regulation and cellular stress, while its inhibition disrupts cell viability and promotes antioxidant gene expression. These results position IDO as a potential therapeutic target for modulating host-pathogen interactions and mitigating nerve damage in leprosy.