Tissue/Biofluid Specific Molecular Cartography of Leishmania donovani Infected BALB/c Mice: Deciphering Systemic Reprogramming.
Tissue/Biofluid Specific Molecular Cartography of Leishmania donovani Infected BALB/c Mice: Deciphering Systemic Reprogramming.
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DOI：
10.3389/fcimb.2021.694470
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发表时间：
2021
影响因子：
5.7
通讯作者：
Shaha C
中科院分区：
文献类型：
--
作者：
Das S;Saha T;Shaha C
内脏利什曼病（VL）的病理生理学尚未完全了解，它已被广泛接受的寄生虫成分和宿主免疫反应都有助于疾病的延续。利什曼病期间的宿主改变是一个薄弱的领域，需要进行更多的探索，以更好地了解VL预后和诊断，这对降低死亡率和感染后后遗症至关重要。为了解决这个问题，我们进行了非靶向代谢组学的杜氏利什曼原虫（Ld）感染，未感染和治疗BALB/c小鼠的组织和生物流体，以阐明宿主代谢组学的变化，使用气相色谱-质谱。单变量和多变量数据处理在几种组织如脑、肝、脾和骨髓中提供了许多显著的差异命中。在LD感染小鼠的血清、尿液和粪便样品中也观察到差异调节，这可以进一步用于生物标志物和诊断验证。在感染（TCA、糖酵解、脂肪酸、嘌呤和嘧啶等）和处理（精氨酸、富马酸、乳清酸、琥珀酸胆碱等）样品中发现几种代谢途径上调/下调。结果还说明了在对照、感染和处理样品以及不同组织/生物液体中具有不同调节模式的几种代谢物;例如，在感染小鼠的血清样品中鉴定出谷氨酸。已鉴定的代谢物包括一系列氨基酸、维生素E、能量相关分子等。此外，已经在各种组织中鉴定了潜在的生物标志物-脑中的精氨酸和富马酸、肝中的胆碱、脾和骨髓中的9-（10）EpOME、骨髓中的N-乙酰腐胺等。在生物体液中，血清中的谷氨酸、尿液中的肼和脱氧核糖以及粪便中的3-甲基-2-氧代戊酸是一些已鉴定的潜在生物标志物。这些代谢物可以进一步研究其在疾病复杂性中的作用或作为预后标志物。所提出的分析方法使我们能够在宿主中VL期间获得个体组织/生物流体调制的代谢画像，并代表用于进一步研究的有价值的系统读数。我们的研究结果提供了一个更好的理解宿主代谢组界面的扰动VL期间，包括许多可能的潜在的诊断和治疗靶点的识别。
Pathophysiology of visceral leishmaniasis (VL) is not fully understood and it has been widely accepted that the parasitic components and host immune response both contribute to the perpetuation of the disease. Host alterations during leishmaniasis is a feebly touched area that needs to be explored more to better understand the VL prognosis and diagnosis, which are vital to reduce mortality and post-infection sequelae. To address this, we performed untargeted metabolomics of Leishmania donovani (Ld) infected, uninfected and treated BALB/c mice’s tissues and biofluids to elucidate the host metabolome changes using gas chromatography–mass spectrometry. Univariate and multivariate data treatments provided numerous significant differential hits in several tissues like the brain, liver, spleen and bone marrow. Differential modulations were also observed in serum, urine and fecal samples of Ld-infected mice, which could be further targeted for biomarker and diagnostic validations. Several metabolic pathways were found to be upregulated/downregulated in infected (TCA, glycolysis, fatty acids, purine and pyrimidine, etcetera) and treated (arginine, fumaric acid, orotic acid, choline succinate, etcetera) samples. Results also illustrated several metabolites with different pattern of modulations in control, infected and treated samples as well as in different tissues/biofluids; for e.g. glutamic acid identified in the serum samples of infected mice. Identified metabolites include a range of amino acids, saccharides, energy-related molecules, etcetera. Furthermore, potential biomarkers have been identified in various tissues—arginine and fumaric acid in brain, choline in liver, 9-(10) EpOME in spleen and bone marrow, N-acetyl putrescine in bone marrow, etcetera. Among biofluids, glutamic acid in serum, hydrazine and deoxyribose in urine and 3-Methyl-2-oxo pentanoic acid in feces are some of the potential biomarkers identified. These metabolites could be further looked into for their role in disease complexity or as a prognostic marker. The presented profiling approach allowed us to attain a metabolic portrait of the individual tissue/biofluid modulations during VL in the host and represent a valuable system readout for further studies. Our outcomes provide an improved understanding of perturbations of the host metabolome interface during VL, including identification of many possible potential diagnostic and therapeutic targets.