结核分枝杆菌Rv2653蛋白通过增强糖酵解促进炎症反应。

IF 1.3 4区 医学 Q4 INFECTIOUS DISEASES
Japanese journal of infectious diseases Pub Date : 2023-11-22 Epub Date: 2023-07-31 DOI:10.7883/yoken.JJID.2022.647
Yaman Du, Rui Zheng, Hongli Yin, Li Ma, Jingfang Li, Yun Chen, Xi Zhang, Pengzuo Tao, Lili Gao, Li Yang, Liang He
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引用次数: 0

摘要

结核分枝杆菌(M.tb)感染导致传染性疾病结核病(TB),这是一种主要疾病,也是全世界死亡的主要原因之一。在结核分枝杆菌中由缺失区(RD)编码的蛋白质通过诱导炎症反应或破坏宿主细胞代谢介导结核分枝杆菌的致病特性。我们从RD13中克隆并纯化了Rv2653蛋白,探讨其对宿主巨噬细胞的调控作用。我们发现Rv2653在人白血病单核细胞(THP1)中促进糖酵解并上调关键糖酵解酶,即己糖激酶2 (HK2)和乳酸脱氢酶a (LDHA)的表达。此外,Rv2653诱导糖酵解有助于激活核苷酸结合结构域,富含亮氨酸的家族,含pyrin结构域-3 (NLRP3)炎症小体。Rv2653激活了哺乳动物雷帕霉素复合物1 (mTORC1)信号通路靶点,mTORC1抑制剂NR1阻断了Rv2653诱导的HK2、LDHA和NLRP3的表达。siRNA干扰HK2或LDHA可显著抑制Rv2653对NLRP3炎症小体的激活,阻断Rv2653引发的炎症因子白细胞介素(IL)-1β、IL-6、肿瘤坏死因子(TNF)-α、活性氧(ROS)、一氧化氮(NO),促进卡介苗(BCG)在THP1细胞中的存活。总的来说,Rv2653通过激活mTORC1信号通路、激活NLRP3炎症小体、释放炎症因子促进糖酵解,最终抑制BCG在THP1细胞内的细胞内存活。因此,我们发现anti-M。Rv2653诱导的tb免疫机制有助于开发新的抗tb策略。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Mycobacterium tuberculosis Rv2653 Protein Promotes Inflammation Response by Enhancing Glycolysis.

Mycobacterium tuberculosis (M.tb) infection causes the communicable disease tuberculosis (TB), a major disease and one of the leading causes of death worldwide. The protein encoded by the region of deletion (RD) in M.tb mediates the pathogenic properties of M.tb by inducing an inflammatory response or disrupting host cell metabolism. We cloned and purified the Rv2653 protein from RD13 to explore its regulatory effects on host macrophages. We found that Rv2653 promoted glycolysis and upregulated the expression of key glycolytic enzymes, namely, hexokinase 2 (HK2) and lactate dehydrogenase-A (LDHA) in human leukemia monocytic (THP1) cells. Furthermore, the induction of glycolysis by Rv2653 contributes to the activation of the nucleotide-binding domain, leucine-rich-containing family, pyrin domain-containing-3 (NLRP3) inflammasome. Rv2653 activated the mammalian target of rapamycin complex 1 (mTORC1) signaling pathway, and the mTORC1 inhibitor NR1 blocked Rv2653-induced HK2, LDHA, and NLRP3 expression. siRNA interfering with HK2 or LDHA significantly inhibited the activation of NLRP3 inflammasome by Rv2653, blocked Rv2653-triggered inflammatory factors interleukin (IL)-1β, IL-6, tumor necrosis factor (TNF)-α, reactive oxygen species (ROS), and nitric oxide (NO), and promoted the survival of Bacillus Calmette-Guerin (BCG) in THP1 cells. Overall, Rv2653 promoted glycolysis by activating the mTORC1 signaling pathway, activating the NLRP3 inflammasome, and releasing inflammatory factors, ultimately inhibiting the intracellular survival of BCG in THP1 cells. Therefore, we revealed that anti-M.tb immune mechanisms induced by Rv2653 contribute to the development of new anti-TB strategies.

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来源期刊
CiteScore
4.50
自引率
4.50%
发文量
172
审稿时长
2 months
期刊介绍: Japanese Journal of Infectious Diseases (JJID), an official bimonthly publication of National Institute of Infectious Diseases, Japan, publishes papers dealing with basic research on infectious diseases relevant to humans in the fields of bacteriology, virology, mycology, parasitology, medical entomology, vaccinology, and toxinology. Pathology, immunology, biochemistry, and blood safety related to microbial pathogens are among the fields covered. Sections include: original papers, short communications, epidemiological reports, methods, laboratory and epidemiology communications, letters to the editor, and reviews.
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