Background The latent TB infection (LTBI) is an asymptomatic infection caused by Mycobacterium tuberculosis (M.bt). Previous studies have shown a host-protective role for Heme oxygenase-1 (HO-1) during Mtb infection and an important involvement of Glutathione peroxidase-4 (Gpx4) in the necrotic pathology of the disease. Furthermore, increasing evidence suggested a crucial role for Glutathione in the granulomatous response to M. tb infection, with altered GSH levels associated to decreased host resistance. The aim of this study was to provide additional tools for discriminating the pathologic TB state and the asymptomatic infection. Methods We analyzed the gene expression of HO-1 and Gpx4 enzymes in blood of subjects with LTBI, active TB and healthy controls, and we also measured blood levels of the reduced (GSH) and oxidized (GSSG) forms of glutathione, together with the evaluation of GCL expression, the gene responsible for the GSH de novo synthesis. Results Our findings highlight a shift of glutathione homeostasis towards a more reducing conditions in LTBI, and a different modulation of GSH-dependent genes and HO-1 expression respect to active TB. Conclusion This study can provide useful tools to understand the redox background that address the infection toward the asymptomatic or active disease.

中文翻译：

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无症状潜伏性人类结核病的氧化还原生物标志物：与活动性疾病的比较

背景 潜伏性结核感染（LTBI）是由结核分枝杆菌（M.bt）引起的无症状感染。先前的研究表明，血红素加氧酶-1 (HO-1) 在 Mtb 感染期间具有宿主保护作用，并且谷胱甘肽过氧化物酶-4 (Gpx4) 在该疾病的坏死病理学中发挥重要作用。此外，越来越多的证据表明谷胱甘肽在结核分枝杆菌感染的肉芽肿反应中发挥着至关重要的作用，谷胱甘肽水平的改变与宿主抵抗力的降低相关。本研究的目的是提供额外的工具来区分病理性结核病状态和无症状感染。方法 我们分析了 LTBI 受试者、活动性结核病受试者和健康对照者血液中 HO-1 和 Gpx4 酶的基因表达，还测量了还原型谷胱甘肽 (GSH) 和氧化型谷胱甘肽 (GSSG) 的血液水平，以及评估 GCL 表达，该基因负责 GSH 从头合成。结果我们的研究结果强调了 LTBI 中谷胱甘肽稳态向更还原条件的转变，以及与活动性结核病相关的 GSH 依赖性基因和 HO-1 表达的不同调节。结论 这项研究可以提供有用的工具来了解氧化还原背景，从而解决无症状或活动性疾病的感染问题。