Centre for Vaccines and Immunology, National Institute for Communicable Diseases, a division of the National Health Laboratory Service, Johannesburg, 2192, South Africa.
Chemical Pathology, School of Pathology, University of the Witwatersrand, Johannesburg, 2193, South Africa.
Bioessays. 2020 May;42(5):e1900220. doi: 10.1002/bies.201900220.
Indoleamine 2,3-dioxygenase (IDO) is the rate-limiting enzyme in conversion of tryptophan to kynurenines, feeding de novo nicotinamide synthesis. IDO orchestrates materno-foetal tolerance, increasing human reproductive fitness. IDO mediates immune suppression through depletion of tryptophan required by T lymphocytes and other mechanisms. IDO is expressed by alternatively activated macrophages, suspected to play a key role in tuberculosis (TB) pathogenesis. Unlike its human host, Mycobacterium tuberculosis can synthesize tryptophan, suggesting possible benefit to the host from infection with the microbe. Intriguingly, nicotinamide analogues are used to treat TB. In reviewing this field, it is postulated that flux through the nicotinamide synthesis pathway reflects switching between aerobic glycolysis and oxidative phosphorylation in M. tuberculosis-infected macrophages. The evolutionary cause of such shifts may be ancient mitochondrial behavior related to reproductive fitness. Evolutionary perspectives on the IDO pathway may elucidate why, after centuries of co-existence with the Tubercle bacillus, humans still remain susceptible to TB disease.
色氨酸 2,3-双加氧酶（IDO）是将色氨酸转化为犬尿氨酸的限速酶，为从头合成烟酰胺提供原料。IDO 协调母胎耐受，提高人类生殖适应性。IDO 通过耗尽 T 淋巴细胞等所需的色氨酸来介导免疫抑制，以及其他机制。IDO 由被激活的巨噬细胞表达，被怀疑在结核病（TB）发病机制中发挥关键作用。与人类宿主不同，结核分枝杆菌可以合成色氨酸，这表明感染微生物可能对宿主有益。有趣的是，烟酰胺类似物被用于治疗结核病。在回顾这一领域时，有人假设烟酰胺合成途径的通量反映了结核分枝杆菌感染的巨噬细胞中需氧糖酵解和氧化磷酸化之间的转换。这种转变的进化原因可能与生殖适应性有关的古老线粒体行为。对 IDO 途径的进化视角可能阐明为什么在与结核分枝杆菌共存了几个世纪之后，人类仍然容易感染结核病。
