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首页> 外文期刊>Infection and immunity >Indoleamine 2,3-Dioxygenase, Tryptophan Catabolism, and Mycobacterium avium subsp. paratuberculosis: a Model for Chronic Mycobacterial Infections
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Indoleamine 2,3-Dioxygenase, Tryptophan Catabolism, and Mycobacterium avium subsp. paratuberculosis: a Model for Chronic Mycobacterial Infections

机译：吲哚胺2，3-二加氧酶，色氨酸分解代谢和鸟分枝杆菌亚种。副结核病：慢性分枝杆菌感染的模型

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Virulent mycobacterial infections progress slowly, with a latent period that leads to clinical disease in a proportion of cases. Mycobacterium avium subsp. paratuberculosis is an intracellular pathogen that causes paratuberculosis or Johne's disease (JD), a chronic intestinal disease of ruminants. Indoleamine 2,3-dioxygenase (IDO), an enzyme that regulates tryptophan metabolism, was originally reported to have a role in intracellular pathogen killing and has since been shown to have an important immunoregulatory role in chronic immune diseases. Here we demonstrate an association between increased IDO levels and progression to clinical mycobacterial disease in a natural host, characterizing gene expression, protein localization, and functional effects. IDO mRNA levels were significantly increased in M. avium subsp. paratuberculosis-infected monocytic cells. Levels of both IDO gene and protein expression were significantly upregulated within the affected tissues of sheep with JD, particularly at the site of primary infection, the ileum, of animals with severe multibacillary disease. Lesion severity was correlated with the level of IDO gene expression. IDO gene expression was also increased in the peripheral blood cells of M. avium subsp. paratuberculosis-exposed sheep and cattle. IDO breaks down tryptophan, and systemic increases were functional, as shown by decreased plasma tryptophan levels, which correlated with the onset of clinical signs, a stage well known to be associated with Th1 immunosuppression. IDO may be involved in downregulating immune responses to M. avium subsp. paratuberculosis and other virulent mycobacteria, which may be an example of the pathogen harnessing host immunoregulatory pathways to aid survival. These findings raise new questions about the host-mycobacterium interactions in the progression from latent to clinical disease.
机译：毒性分枝杆菌感染进展缓慢，潜伏期导致一定比例的临床疾病。鸟分枝杆菌亚种副结核病是引起副结核病或约翰内斯病（JD）（反刍动物的慢性肠道疾病）的一种细胞内病原体。吲哚胺2，3-二加氧酶（IDO）是一种调节色氨酸代谢的酶，最初被报道在细胞内病原体杀灭中起作用，并且自那以后已显示出在慢性免疫疾病中具有重要的免疫调节作用。在这里，我们证明了在天然宿主中IDO水平升高与临床分枝杆菌疾病进展之间的关联，表征了基因表达，蛋白质定位和功能作用。 IDO mRNA水平在鸟分枝杆菌亚种中显着增加。副结核病感染的单核细胞。在患有JD的绵羊的受影响组织内，特别是在患有严重多细菌性疾病的动物的原发感染部位，回肠处，IDO基因和蛋白质表达水平均显着上调。病变严重程度与IDO基因表达水平相关。在鸟分枝杆菌亚种的外周血细胞中IDO基因表达也增加。暴露于副结核病的绵羊和牛。 IDO分解色氨酸，全身功能正常，如血浆色氨酸水平降低所显示，血浆色氨酸水平与临床体征的发作相关，临床体征与Th1免疫抑制有关。 IDO可能参与下调对鸟分枝杆菌亚种的免疫反应。副结核病和其他有毒力的分枝杆菌，可能是病原体利用宿主免疫调节途径帮助生存的一个例子。这些发现提出了从隐性疾病到临床疾病过程中宿主-分枝杆菌相互作用的新问题。

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