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.

中文翻译：

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结核病的进化观点：吲哚胺 2,3-双加氧酶催化的烟酰胺合成反映了巨噬细胞代谢的变化：吲哚胺 2,3-双加氧酶反映了结核病发病过程中巨噬细胞代谢的改变。

吲哚胺 2,3-双加氧酶 (IDO) 是色氨酸转化为犬尿氨酸的限速酶，促进烟酰胺从头合成。IDO 协调母胎耐受性，提高人类生殖健康。IDO 通过消耗 T 淋巴细胞所需的色氨酸和其他机制介导免疫抑制。IDO 由交替激活的巨噬细胞表达，怀疑在结核病 (TB) 发病机制中起关键作用。与人类宿主不同，结核分枝杆菌可以合成色氨酸，这表明微生物感染可能对宿主有益。有趣的是，烟酰胺类似物用于治疗结核病。在回顾该领域时，假设通过烟酰胺合成途径的通量反映了 M. 有氧糖酵解和氧化磷酸化之间的转换。结核感染的巨噬细胞。这种转变的进化原因可能是与生殖健康相关的古老线粒体行为。IDO 通路的进化观点可能会阐明为什么在与结核杆菌共存数百年后，人类仍然容易感染结核病。