4.7 Article

Notch4 Negatively Regulates the Inflammatory Response to Mycobacterium tuberculosis Infection by Inhibiting TAK1 Activation

Journal

JOURNAL OF INFECTIOUS DISEASES
Volume 218, Issue 2, Pages 312-323

Publisher

OXFORD UNIV PRESS INC
DOI: 10.1093/infdis/jix636

Keywords

Mycobacterium tuberculosis; inflammation; macrophage; Notch4; TAK1

Funding

  1. National Natural Science Foundation of China [81101217, 81330069, 91542111, 31730025]
  2. Chinese National Program on Key Basic Research Project [2017YFA0505900]
  3. Science and Technology Commission of Shanghai Municipality [16ZR1428800]

Ask authors/readers for more resources

Tuberculosis, caused by Mycobacterium tuberculosis infection, remains a global threat to human health, but knowledge of the molecular mechanisms underlying the pathogenesis of tuberculosis is still limited. Although Notch4, a member of the Notch receptor family, is involved in the initiation of mammary tumors, its function in M. tuberculosis infection remains unclear. In this study, we found that Notch4-deficient mice were more resistant to M. tuberculosis infection, with a much lower bacterial burden and fewer pathological changes in the lungs. Notch4 inhibited M. tuberculosis-induced production of proinflammatory cytokines by interaction with TAK1 and inhibition of its activation. Furthermore, we found that Notch intracellular domain 4 prevented TRAF6 autoubiquitination and suppressed TRAF6-mediated TAK1 polyubiquitination. Finally, Notch inhibitors made mice more resistant to M. tuberculosis infection. These results suggest that Notch4 is a negative regulator of M. tuberculosis-induced inflammatory response, and treatment with a Notch inhibitor could serve as a new therapeutic strategy for tuberculosis.

Authors

I am an author on this paper
Click your name to claim this paper and add it to your profile.

Reviews

Primary Rating

4.7
Not enough ratings

Secondary Ratings

Novelty
-
Significance
-
Scientific rigor
-
Rate this paper

Recommended

Article Neurosciences

Essential Role of Sptan1 in Cochlear Hair Cell Morphology and Function Via Focal Adhesion Signaling

Qingxiu Yao, Hui Wang, Hengchao Chen, Zhuangzhuang Li, Yumeng Jiang, Zhipeng Li, Jiping Wang, Yazhi Xing, Feng Liu, Dongzhen Yu, Shankai Yin

Summary: The study identified SPTAN1 as a critical molecule for HC stereocilia morphology and auditory function through regulation of focal adhesion signaling. Sptan1 deficiency in mice led to deafness, abnormal formation of stereocilia and cuticular plates.

MOLECULAR NEUROBIOLOGY (2022)

Article Endocrinology & Metabolism

Effects of Chronic Intermittent Hypoxia and Chronic Sleep Fragmentation on Gut Microbiome, Serum Metabolome, Liver and Adipose Tissue Morphology

Fan Wang, Juanjuan Zou, Huajun Xu, Weijun Huang, Xiaoman Zhang, Zhicheng Wei, Xinyi Li, Yupu Liu, Jianyin Zou, Feng Liu, Huaming Zhu, Hongliang Yi, Jian Guan, Shankai Yin

Summary: Chronic intermittent hypoxia and chronic sleep fragmentation are two main pathological features of obstructive sleep apnea. This study found correlations between intestinal microbiota, metabolites, and lipid metabolism under conditions of CIH or CSF, which affected adipose tissue and hepatic lipid metabolism.

FRONTIERS IN ENDOCRINOLOGY (2022)

Article Genetics & Heredity

Comprehensive Analysis of N6-Methyladenosine Regulators in the Subcluster Classification and Drug Candidates Prediction of Severe Obstructive Sleep Apnea

Niannian Li, Zhenfei Gao, Jinhong Shen, Yuenan Liu, Kejia Wu, Jundong Yang, Shengming Wang, Xiaoman Zhang, Yaxin Zhu, Jingyu Zhu, Jian Guan, Feng Liu, Shankai Yin

Summary: The study investigates the impact of m6A modification in severe OSA, identifying dysregulated m6A regulators in severe OSA patients and proposing tailored treatment strategies based on different subclusters. Functional analysis and assessment of immune response activity provide critical insights for future research and treatment options.

FRONTIERS IN GENETICS (2022)

Article Chemistry, Multidisciplinary

Integrative Proteome and Ubiquitinome Analyses Reveal the Substrates of BTBD9 and Its Underlying Mechanism in Sleep Regulation

Zhenfei Gao, Anzhao Wang, Yongxu Zhao, Xiaoxu Zhang, Xiangshan Yuan, Niannian Li, Chong Xu, Shenming Wang, Yaxin Zhu, Jingyu Zhu, Jian Guan, Feng Liu, Shankai Yin

Summary: This study identified the substrates of BTBD9-mediated ubiquitination through proteomic analysis and ubiquitinome analysis. Among the potential substrates, IMPDH2 was identified as a novel target and may be associated with sleep dysregulation.

ACS OMEGA (2022)

Article Pathology

Single-Cell RNA-Seq Reveals Heterogeneity of Cell Communications between Schwann Cells and Fibroblasts within Vestibular Schwannoma Microenvironment

Maoxiang Xu, Shengming Wang, Yumeng Jiang, Jingjing Wang, Yuanping Xiong, Wenqi Dong, Qingxiu Yao, Yazhi Xing, Feng Liu, Zhengnong Chen, Dongzhen Yu

Summary: Single-cell RNA sequencing was used to analyze the cellular composition of vestibular schwannomas (VSs) and investigate the intercellular communication between Schwann cells (SCs) and tumor-associated fibroblasts. The study identified heterogeneous SC subtypes and revealed an important role of integrin and growth factor signaling in the communication between SCs and fibroblasts. These findings provide insights into the development of VSs.

AMERICAN JOURNAL OF PATHOLOGY (2022)

Article Engineering, Electrical & Electronic

High-Power Yb-Doped and All Fiber-Based Nanosecond MOPA Laser

Yiming Cai, Qixin Zhu, Jianhong Shi, Cheng Li, Dapeng Yan, Jinyan Li, Yingbin Xing

Summary: We present the results of high-power laser output obtained using a 300-mu m-core-diameter Yb-doped fiber. With the use of an all-fiber construction and pulse control system, this laser system achieves high performance in terms of average power and peak power, setting a new record.

IEEE PHOTONICS JOURNAL (2022)

Article Multidisciplinary Sciences

Extracellular fibrinogen-binding protein released by intracellular Staphylococcus aureus suppresses host immunity by targeting TRAF3

Xiaokai Zhang, Tingrong Xiong, Lin Gao, Yu Wang, Luxuan Liu, Tian Tian, Yun Shi, Jinyong Zhang, Zhuo Zhao, Dongshui Lu, Ping Luo, Weijun Zhang, Ping Cheng, Haiming Jing, Qiang Gou, Hao Zeng, Dapeng Yan, Quanming Zou

Summary: This study reveals a previously unrecognized mechanism by which Staphylococcus aureus suppresses host defense, involving the secretion of extracellular fibrinogen-binding protein (Efb) into macrophages. Efb disrupts the formation of the TRAF3/TRAF2/cIAP1 complex, leading to the suppression of the inflammatory signaling cascade and decreased pathogenicity.

NATURE COMMUNICATIONS (2022)

Article Chemistry, Multidisciplinary

In Situ Embedding Hydrogen-Bonded Organic Frameworks Nanocrystals in Electrospinning Nanofibers for Ultrastable Broad-Spectrum Antibacterial Activity

Yao Wang, Ran Cao, Chen Wang, Xiyu Song, Ruina Wang, Jiacun Liu, Mengmeng Zhang, Junyi Huang, Tingting You, Yihua Zhang, Dapeng Yan, Wendong Han, Lan Yan, Jisheng Xiao, Peng Li

Summary: A method for preparing highly effective and sustainable antimicrobial nanofibers is reported, which embeds photoactive hydrogen-bonded organic framework (HOF) of rod-like nanocrystals. The resulting nanofibers exhibit excellent tensile and breathability characteristics while protecting HOF nanocrystals against corrosion. By optimizing the amount and type of embedded nanocrystals, the efficiency of singlet oxygen (O-1(2)) generation is improved. The HOF@PVDF-HFP nanofibers demonstrate highly effective killing of pathogens, including viruses, bacteria, and fungi, within 30 minutes under ambient light conditions.

ADVANCED FUNCTIONAL MATERIALS (2023)

Article Cell Biology

Glutamylation of an HIV-1 protein inhibits the immune response by hijacking STING

Gui Qian, Yihua Zhang, Yinan Liu, Manman Li, Bowen Xin, Wenyi Jiang, Wendong Han, Yu Wang, Xian Tang, Liuyan Li, Lingyan Zhu, Tao Sun, Bo Yan, Yongtang Zheng, Jianqing Xu, Baoxue Ge, Zheng Zhang, Dapeng Yan

Summary: Cyclic GMP-AMP synthase (cGAS) recognizes Y-form cDNA of HIV-1 and initiates antiviral immune response, but the p6 protein of HIV-1 suppresses IFN-I expression and promotes immune evasion. Glutamylated p6 inhibits STING interaction with TRIM32 or AMFR, suppressing STING activation by inhibiting K27 and K63 polyubiquitination at K337. CoCl2, a CCP agonist, counteracts p6 glutamylation and inhibits HIV-1 immune evasion.

CELL REPORTS (2023)

Article Cell Biology

Pharmacological boosting of cGAS activation sensitizes chemotherapy by enhancing antitumor immunity

Haipeng Liu, Hang Su, Fei Wang, Yifang Dang, Yijiu Ren, Shenyi Yin, Huinan Lu, Hang Zhang, Jun Wu, Zhu Xu, Mengge Zheng, Jiani Gao, Yajuan Cao, Junfang Xu, Li Chen, Xiangyang Wu, Mingtong Ma, Long Xu, Fang Wang, Jianxia Chen, Chunxia Su, Chunyan Wu, Huikang Xie, Jijie Gu, Jianzhong Jeff Xi, Baoxue Ge, Yiyan Fei, Chang Chen

Summary: Enhancing chemosensitivity is a critical need in cancer therapy. Through a screening process, we have identified brivanib as a modulator of cGAS, which enhances the immune response in tumor cells treated with platinum-based chemotherapeutics. This finding suggests the potential of combining brivanib with platinum-based drugs for cancer treatment.

CELL REPORTS (2023)

Article Neurosciences

FKBP5 genetic variants are associated with respiratory- and sleep-related parameters in Chinese patients with obstructive sleep apnea

Anzhao Wang, Zhicheng Wei, Haolin Yuan, Yaxin Zhu, Yu Peng, Zhenfei Gao, Yuenan Liu, Jinhong Shen, Huajun Xu, Jian Guan, Shankai Yin, Feng Liu, Xinyi Li

Summary: This study investigates the association of single nucleotide polymorphisms (SNPs) in the FKBP5 gene with obstructive sleep apnea (OSA) and OSA-related traits. The results show that four SNPs in the FKBP5 gene are associated with sleep respiratory events in patients with moderate-to-severe OSA during REM sleep, as well as sleep architecture variables in men with moderate OSA. FKBP5 variants may be a potential predisposing factor for sleep disorders.

FRONTIERS IN NEUROSCIENCE (2023)

Article Physics, Multidisciplinary

Flexible beam delivery of ultrafast laser through vacuum-pumped anti-resonant hollow-core fiber

Yiming Cai, Yifan Mai, Shen Xiang, Jianhong Shi, Qixin Zhu, Rong Li, Jinyan Li, Cheng Li, Dapeng Yan, Yingbin Xing

Summary: In this study, we successfully transmitted a 100 MW-peak-power ultrafast laser through a 5-m anti-resonant hollow-core fiber (AR-HCF) with a pumpable armored tube for air exhaust. The results highlight the significance of controlling air concentration in achieving high transmission efficiency and pulse quality.

FRONTIERS IN PHYSICS (2023)

Article Immunology

Mycobacterium tuberculosis suppresses APLP2 expression to enhance its survival in macrophage

Jianxia Chen, Fen Tang, Haohao Li, Xiangyang Wu, Yong Yang, Zhonghua Liu, Xiaochen Huang, Jie Wang, Ruijuan Zheng, Lin Wang, Haipeng Liu, Junfang Xu, Peng Wang, Feng Liu

Summary: This study reveals a significant decrease in Aplp2 levels in TB patients, M.tb-infected macrophages, and mice. Knockdown or mutation of Aplp2 leads to reduced macrophage-mediated killing of M.tb, accompanied by decreased expression of iNOS and reduced cytokine production. Aplp2 mutant mice show increased susceptibility to mycobacterial infection.

INTERNATIONAL IMMUNOPHARMACOLOGY (2023)

Letter Biochemistry & Molecular Biology

Promotion of liquid-to-solid phase transition of cGAS by Baicalein suppresses lung tumorigenesis

Tiansheng Zheng, Haipeng Liu, Yifan Hong, Yajuan Cao, Qing Xia, Chengge Qin, Ming Li, Russel J. J. Reiter, Yidong Bai, Lihong Fan

SIGNAL TRANSDUCTION AND TARGETED THERAPY (2023)

Article Biochemical Research Methods

Identification of phosphorylation site on PARP1 mediating its cytosolic translocation in virus-infected HeLa cells

Fei Wang, Ming Tong Ma, Junfang Xu, Haipeng Liu

Summary: The protocol describes a method to monitor PARP1 subcellular localization and details steps to identify phosphorylation sites on PARP1. This has implications for studying protein phosphorylation events in other cell types.

STAR PROTOCOLS (2022)

No Data Available