Immunometabolic changes in macrophages in response to house dust mite extract

Q4 Medicine
T. Yurakova, E. Gorshkova, M. A. Nosenko, E. Gubernatorova, M. Drutskaya
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引用次数: 0

Abstract

To date, much remains unclear about the pathogenesis of asthma, one of the most common chronic and highly heterogenic diseases of the respiratory system. The lack of specific and highly effective therapy in case of certain asthma subtypes requires the search for new approaches to treatment. One possible approach would be to influence the metabolism and immune functions of myeloid cells. This approach finds its application in the treatment of cancer and other diseases in the pathogenesis of which macrophages play an important role. It was shown that the pathogenesis of allergic asthma in response to one of the most common allergens, house dust mite, is due to a metabolic TNF-mediated reprogramming of alveolar macrophages. This suggests that influencing the process of TNF production or metabolic adaptations with specific blockers may also lead to a reduction in the symptoms of the course of the disease as a whole. In this work, we experimentally tested whether the previously obtained phenotype that occurs in macrophages in response to HDM cultured in DMEM is preserved if cells are cultured under more physiologically relevant conditions: in a medium closely related in composition to blood plasma. We also analyzed open databases of alveolar macrophages sequencing obtained from patients with asthma or from the lungs of mice in an HDM-induced asthma model in order to correlate specific immunometabolic changes. It was found that macrophages cultured under conditions close to physiological, simultaneously increase the rates of respiration and glycolysis, and also produce TNF in response to HDM. The observed phenotype is consistent with transcriptomic analyzes performed on human and mouse samples, which revealed an increase in the expression of genes related to glycolysis, oxidative phosphorylation, and the TNF signaling pathway. Thus, the data confirm the relevance of the phenotype obtained in vitro to the changes occurring in the in vivo system. However, functional verification at the level of metabolites, proteins and changes in metabolic activity is also required. In addition, it remains to be established how the blocking of individual metabolic pathways affects the features of the functional macrophage phenotype that occurs in response to HDM, and whether this effect can alleviate asthma symptoms.
屋尘螨提取物对巨噬细胞免疫代谢的影响
迄今为止,关于哮喘的发病机制仍不清楚,哮喘是呼吸系统最常见的慢性和高度异质性疾病之一。由于某些哮喘亚型缺乏特异性和高效的治疗方法,需要寻找新的治疗方法。一种可能的方法是影响骨髓细胞的代谢和免疫功能。这种方法在癌症和其他巨噬细胞在其发病机制中起重要作用的疾病的治疗中得到了应用。研究表明,过敏性哮喘对一种最常见的过敏原——室内尘螨的反应,其发病机制是由于代谢性tnf介导的肺泡巨噬细胞重编程。这表明,用特定阻滞剂影响TNF的产生过程或代谢适应也可能导致整个疾病过程中症状的减少。在这项工作中,我们通过实验测试了如果细胞在与血浆成分密切相关的培养基中培养,在DMEM中培养的巨噬细胞中发生的先前获得的HDM应答表型是否保留。我们还分析了从哮喘患者或hdm诱导哮喘模型小鼠肺中获得的肺泡巨噬细胞测序的开放数据库,以关联特异性免疫代谢变化。研究发现,在接近生理条件下培养的巨噬细胞,同时增加呼吸和糖酵解的速率,并产生TNF以响应HDM。观察到的表型与在人和小鼠样本上进行的转录组学分析一致,后者显示糖酵解、氧化磷酸化和TNF信号通路相关基因的表达增加。因此,这些数据证实了体外获得的表型与体内系统中发生的变化的相关性。然而,还需要在代谢物、蛋白质和代谢活动变化水平上进行功能验证。此外,个体代谢途径的阻断如何影响HDM反应中发生的功能性巨噬细胞表型特征,以及这种影响是否可以缓解哮喘症状,仍有待研究。
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来源期刊
Medical Immunology (Russia)
Medical Immunology (Russia) Medicine-Immunology and Allergy
CiteScore
0.70
自引率
0.00%
发文量
88
审稿时长
12 weeks
期刊介绍: The journal mission is to promote scientific achievements in fundamental and applied immunology to various medical fields, the publication of reviews, lectures, essays by leading domestic and foreign experts in the field of fundamental and experimental immunology, clinical immunology, allergology, immunodiagnostics and immunotherapy of infectious, allergy, autoimmune diseases and cancer.
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