miRNA在结核病中对巨噬细胞免疫反应影响的研究进展
Research Progress on the Effect of miRNA on the Immune Response of Macrophages in Tuberculosis
DOI: 10.12677/ACM.2023.1381829, PDF,   
作者: 黄飞扬：青海大学研究生院，青海 西宁；久 太：青海大学附属医院呼吸与危重症学科，青海 西宁
关键词: 结核病；miRNA；先天免疫细胞反应；M1/M2型巨噬细胞；生物标志物；Tuberculosis； miRNA； Innate Immune Cell Response； M1/M2 Macrophages； Biomarker
摘要: 结核分枝杆菌(Mycobacterium tuberculosis, Mtb)是结核病(Tuberculosis, TB)的病原菌，侵入人体后巨噬细胞是结核分枝杆菌主要固有免疫细胞，巨噬细胞(Macrophage, Mø)具有高度的异质性和可塑性，在不同的刺激下可极化成M1、M2型巨噬细胞。外泌体作为细胞及器官间通讯的介质，将其内包含的microRNA等信号因子传递到各个细胞或器官影响其功能活动，有研究表明微小RNA (mi-croRNA, miRNA)参与了抑制细胞凋亡、自噬及细胞因子分泌等先天免疫细胞反应，同时miRNA可通过调节巨噬细胞极化趋势，影响结核杆菌的清除效率。本综述描述了结核分枝杆菌感染后外泌体来源的miRNA参与机体免疫反应，包括参与炎症、细胞凋亡、自噬以及调节巨噬细胞极化对结核杆菌影响的研究进展，还阐述了外泌体miRNA作为诊断或治疗结核病的一种新型标志物的潜力性。
Abstract: Mycobacterium tuberculosis (Mtb) is the pathogen of tuberculosis (TB). Macrophages are the main innate immune cells of Mycobacterium tuberculosis after invading human body. Macrophages are highly heterogeneous and plastic, and can be polarized into M1 and M2 macrophages under differ-ent stimuli. As a communication medium between cells and organs, exosomes transmit signal fac-tors such as microRNA to various cells or organs, which affects their functional activities. Studies have shown that MicroRNA is involved in inhibiting innate immune cell reactions such as apoptosis, autophagy and cytokine secretion, and at the same time, miRNA can affect the clearance efficiency of Mycobacterium tuberculosis by regulating the polarization trend of macrophages. This review describes the progress of research on the role of exosome-derived miRNA in the immune response to Mycobacterium tuberculosis infection, including inflammation, apoptosis, autophagy, and regula-tion of macrophage polarization on Mycobacterium tuberculosis. It also describes the potential of exosomal miRNA as a new marker for the diagnosis or treatment of tuberculosis.
文章引用：黄飞扬, 久太. miRNA在结核病中对巨噬细胞免疫反应影响的研究进展[J]. 临床医学进展, 2023, 13(8): 13057-13066. https://doi.org/10.12677/ACM.2023.1381829

参考文献

[1] World Health Organization (2021) Global Tuberculosis Report 2021.
https://www.who.int/publications/digital/global-tuberculosis-report-2021
[2] 卢春容, 房宏霞, 陆普选, 等. WHO 2021年全球结核病报告: 全球与中国关键数据分析[J]. 新发传染病电子杂志, 2021, 6(4): 368-372.
[3] Ahmad, F., Rani, A., Alam, A., et al. (2022) Macrophage: A Cell with Many Faces and Functions in Tu-berculosis. Frontiers in Immunology, 13, Article ID: 747799. [Google Scholar] [CrossRef] [PubMed]
[4] Epelman, S., Lavine, K.J. and Randolph, G.J. (2014) Origin and Functions of Tissue Macrophages. Immunity, 41, 21-35. [Google Scholar] [CrossRef] [PubMed]
[5] Atri, C., Guerfali, F.Z. and Laouini, D. (2018) Role of Human Macrophage Polarization in Inflammation during Infectious Diseases. International Journal of Molecular Sciences, 19, 1801. [Google Scholar] [CrossRef] [PubMed]
[6] Zeng, H., Zhao, B., Zhang, D., et al. (2022) Viola Yedoensis Makino Formula Alleviates DNCB-Induced Atopic Dermatitis by Activating JAK2/STAT3 Signaling Pathway and Promoting M2 Macrophages Polarization. Phytomedicine, 103, Article ID: 154228. [Google Scholar] [CrossRef] [PubMed]
[7] Xu, L., Wang, L., Yang, R., et al. (2023) Lung Adenocarcinoma Cell-Derived Exosomes Promote M2 Macrophage Polarization through Transmission of miR-3153 to Activate the JNK Signaling Pathway. Human Molecular Genetics, 32, 2162-2176. [Google Scholar] [CrossRef] [PubMed]
[8] Li, G.L., Tang, J.F., Tan, W.L., et al. (2023) The Anti-Hepatocellular Carcinoma Effects of Polysaccharides from Ganoderma lucidum by Regulating Macrophage Polarization via the MAPK/NF-κB Signaling Pathway. Food & Function, 14, 3155-3168. [Google Scholar] [CrossRef] 
[9] Wang, Y., Zhang, X., Wang, J., et al. (2023) Inflammatory Periodontal Ligament Stem Cells Drive M1 Macrophage Polarization via Exosomal miR-143-3p-Mediated Regulation of PI3K/AKT/NF-κB Signaling. Stem Cells, 41, 184-199. [Google Scholar] [CrossRef] [PubMed]
[10] 赵九洲, 姜晓旭, 李宏伟, 等. JAK-STAT信号通路与巨噬细胞炎症调控的研究进展[J]. 癌变∙畸变∙突变, 2020, 32(5): 402-404.
[11] Niehues, H., Rösler, B., van der Krieken, D.A., et al. (2019) STAT1 Gain-of-Function Compromises Skin Host Defense in the Context of IFN-γ Signaling. Journal of Al-lergy and Clinical Immunology, 143, 1626-1629.e5. [Google Scholar] [CrossRef] [PubMed]
[12] Oh, H., Park, S.H., Kang, M.K., et al. (2019) Asaronic Acid Atten-uates Macrophage Activation toward M1 Phenotype through Inhibition of NF-κB Pathway and JAK-STAT Signaling in Glucose-Loaded Murine Macrophages. Journal of Agricultural and Food Chemistry, 67, 10069-10078. [Google Scholar] [CrossRef] [PubMed]
[13] Luan, G., Pan, F., Bu, L., et al. (2021) Butorphanol Promotes Mac-rophage Phenotypic Transition to Inhibit Inflammatory Lung Injury via κ Receptors. Frontiers in Immunology, 12, Arti-cle ID: 692286. [Google Scholar] [CrossRef] [PubMed]
[14] Liu, Y., Wang, L., Li, S., et al. (2022) Mechanical Stimulation Improves Rotator Cuff Tendon-Bone Healing via Activating IL-4/JAK/STAT Signaling Pathway Mediated Macrophage M2 Polarization. Journal of Orthopaedic Translation, 37, 78-88. [Google Scholar] [CrossRef] [PubMed]
[15] Essandoh, K., Li, Y., Huo, J., et al. (2016) MiRNA-Mediated Mac-rophage Polarization and Its Potential Role in the Regulation of Inflammatory Response. Shock, 46, 122-131. [Google Scholar] [CrossRef] 
[16] Labonte, A.C., Tosello-Trampont, A.C. and Hahn, Y.S. (2014) The Role of Macrophage Polarization in Infectious and Inflammatory Diseases. Molecules and Cells, 37, 275-285. [Google Scholar] [CrossRef] [PubMed]
[17] Koh, Y.C., Yang, G., Lai, C.S., et al. (2018) Chemopreventive Effects of Phytochemicals and Medicines on M1/M2 Polarized Macrophage Role in Inflammation-Related Diseases. In-ternational Journal of Molecular Sciences, 19, Article No. 2208. [Google Scholar] [CrossRef] [PubMed]
[18] Cho, H.J., Lim, Y.J., Kim, J., et al. (2020) Different Macrophage Polarization between Drug-Susceptible and Multi-drug-Resistant Pulmonary Tuberculosis. BMC Infectious Diseases, 20, Article No. 81. [Google Scholar] [CrossRef] [PubMed]
[19] Rao, X., Zhou, X., Wang, G., et al. (2022) NLRP6 Is Required for Cancer-Derived Exosome-Modified Macrophage M2 Polarization and Promotes Metastasis in Small Cell Lung Can-cer. Cell Death & Disease, 13, Article No. 891. [Google Scholar] [CrossRef] [PubMed]
[20] Kong, Y. and Guo, L. (2023) Sunitinib Suppresses M2 Polariza-tion of Macrophages in Tumor Microenvironment to Regulate Hepatocellular Carcinoma Progression. Journal of Bio-chemical and Molecular Toxicology, 16, e23333. [Google Scholar] [CrossRef] [PubMed]
[21] Cheruku, S., Rao, V., Pandey, R., et al. (2023) Tumor-Associated Macro-phages Employ Immunoediting Mechanisms in Colorectal Tumor Progression: Current Research in Macrophage Re-polarization Immunotherapy. International Immunopharmacology, 116, Article ID: 109569. [Google Scholar] [CrossRef] [PubMed]
[22] Purghè, B., Manfredi, M., Ragnoli, B., et al. (2021) Exosomes in Chronic Respiratory Diseases. Biomedicine & Pharmacotherapy, 144, Article ID: 112270. [Google Scholar] [CrossRef] [PubMed]
[23] 冯真, 张博, 邓思齐, 等. 血浆外泌体miR-26a-5p和miR-151a-3p在结核病中的表达及诊断价值[J]. 安徽医科大学学报, 2022, 57(12): 1979-1984.
[24] Fabbri, M., Paone, A., Calore, F., et al. (2012) MicroRNAs Bind to Toll-Like Receptors to Induce Prometastatic Inflammatory Re-sponse. Proceedings of the National Academy of Sciences of the United States of America, 109, E2110-E2116. [Google Scholar] [CrossRef] [PubMed]
[25] Pan, B.T., Teng, K., Wu, C., et al. (1985) Electron Microscopic Ev-idence for Externalization of the Transferrin Receptor in Vesicular Form in Sheep Reticulocytes. Journal of Cell Biology, 101, 942-948. [Google Scholar] [CrossRef] [PubMed]
[26] 高舒颖, 梁爽, 刘永军, 等. 外泌体在基因递送系统中的研究进展[J]. 中国医药工业杂志, 2023, 54(3): 295-303.
[27] Rashed, M., Bayraktar, E., Helal, G., et al. (2017) Exosomes: From Garbage Bins to Promising Therapeutic Targets. International Journal of Molecular Sciences, 18, Article No. 538. [Google Scholar] [CrossRef] [PubMed]
[28] Alipoor, S.D., Mortaz, E., Garssen, J., et al. (2016) Exosomes and Ex-osomal miRNA in Respiratory Diseases. Mediators of Inflammation, 2016, Article ID: 5628404. [Google Scholar] [CrossRef] [PubMed]
[29] Li, X., He, J., Wang, G., et al. (2021) Diagnostic Value of mi-croRNA-155 in Active Tuberculosis: A Systematic Review and Meta-Analysis. Medicine (Baltimore), 100, e27869. [Google Scholar] [CrossRef] 
[30] Kim, J., Park, H., Park, S.B., et al. (2022) Identification of MicroRNAs as Potential Blood-Based Biomarkers for Diagnosis and Therapeutic Monitoring of Active Tuberculosis. Diagnostics (Basel), 12, Article No. 369. [Google Scholar] [CrossRef] [PubMed]
[31] Alipoor, S.D., Tabarsi, P., Varahram, M., et al. (2019) Serum Exosomal miRNAs Are Associated with Active Pulmonary Tuberculosis. Disease Markers, 2019, Article ID: 1907426. [Google Scholar] [CrossRef] [PubMed]
[32] Ndzi, E.N., Nkenfou, C.N., Mekue, L.M., et al. (2019) MicroRNA hsa-miR-29a-3p Is a Plasma Biomarker for the Differential Diagnosis and Monitoring of Tuberculosis. Tuberculosis (Edinb), 114, 69-76. [Google Scholar] [CrossRef] [PubMed]
[33] Sinigaglia, A., Peta, E., Riccetti, S., et al. (2020) Tuberculo-sis-Associated MicroRNAs: From Pathogenesis to Disease Biomarkers. Cells, 9, Article No. 2160. [Google Scholar] [CrossRef] [PubMed]
[34] Liang, S., Ma, J., Gong, H., et al. (2022) Immune Regulation and Emerging Roles of Noncoding RNAs in Mycobacterium tuberculosis Infection. Frontiers in Immunology, 13, Article ID: 987018. [Google Scholar] [CrossRef] [PubMed]
[35] Ouimet, M., Koster, S., Sakowski, E., et al. (2016) Mycobacte-rium tuberculosis Induces the miR-33 Locus to Reprogram Autophagy and Host Lipid Metabolism. Nature Immunology, 17, 677-686. [Google Scholar] [CrossRef] [PubMed]
[36] Chen, D.Y., Chen, Y.M., Lin, C.F., et al. (2020) Mi-croRNA-889 Inhibits Autophagy to Maintain Mycobacterial Survival in Patients with Latent Tuberculosis Infection by Targeting TWEAK. mBio, 11, e03045-19. [Google Scholar] [CrossRef] 
[37] Tu, H., Yang, S., Jiang, T., et al. (2019) Elevated Pulmonary Tuber-culosis Biomarker miR-423-5p Plays Critical Role in the Occurrence of Active TB by Inhibiting Autophago-some-Lysosome Fusion. Emerging Microbes & Infections, 8, 448-460. [Google Scholar] [CrossRef] [PubMed]
[38] Gu, X., Gao, Y., Mu, D.G., et al. (2017) MiR-23a-5p Mod-ulates Mycobacterial Survival and Autophagy during Mycobacterium tuberculosis Infection through TLR2/MyD88/NF-κB Pathway by Targeting TLR2. Experimental Cell Research, 354, 71-77. [Google Scholar] [CrossRef] [PubMed]
[39] Dong, W., Wang, G., Feng, J., et al. (2022) MiR-25 Blunts Au-tophagy and Promotes the Survival of Mycobacterium tuberculosis by Regulating NPC1. iScience, 25, Article ID: 104279. [Google Scholar] [CrossRef] [PubMed]
[40] Liu, F., Chen, J., Wang, P., et al. (2018) MicroRNA-27a Controls the Intracellular Survival of Mycobacterium tuberculosis by Regulating Calcium-Associated Autophagy. Nature Communications, 9, Article No. 4295. [Google Scholar] [CrossRef] [PubMed]
[41] Liu, K., Hong, D., Zhang, F., et al. (2020) MicroRNA-106a In-hibits Autophagy Process and Antimicrobial Responses by Targeting ULK1, ATG7, and ATG16L1 During Mycobacte-rial Infection. Frontiers in Immunology, 11, Article ID: 610021. [Google Scholar] [CrossRef] [PubMed]
[42] Wang, Y., Chen, C., Xu, X.D., et al. (2020) Levels of miR-125a-5p Are Altered in Mycobacterium avium-Infected Macrophages and Associate with the Triggering of an Au-tophagic Response. Microbes and Infection, 22, 31-39. [Google Scholar] [CrossRef] [PubMed]
[43] Li, W.T. and Zhang, Q. (2019) MicroRNA-708-5p Regulates Mycobacterial Vitality and the Secretion of Inflammatory Factors in Mycobacterium tuberculosis-Infected Macrophages by Targeting TLR4. European Review for Medical and Pharmacological Sciences, 23, 8028-8038.
[44] Singh, Y., Kaul, V., Mehra, A., et al. (2013) Mycobacterium tuberculosis Controls microRNA-99b (miR-99b) Expression in Infected Murine Dendritic Cells to Modulate Host Immunity. Journal of Biological Chemistry, 288, 5056-5061. [Google Scholar] [CrossRef] 
[45] Liu, F., Dong, Z., Lin, Y., et al. (2021) MicroRNA-502-3p Pro-motes Mycobacterium tuberculosis Survival in Macrophages by Modulating the Inflammatory Response by Targeting ROCK1. Molecular Medicine Reports, 24, Article No. 753. [Google Scholar] [CrossRef] [PubMed]
[46] Zhang, Z.M., Zhang, A.R., Xu, M., et al. (2017) TLR-4/miRNA-32-5p/FSTL1 Signaling Regulates Mycobacterial Survival and Inflammatory Responses in Mycobacterium tuberculosis-Infected Macrophages. Experimental Cell Research, 352, 313-321. [Google Scholar] [CrossRef] [PubMed]
[47] Vereecke, L., Beyaert, R. and van Loo, G. (2009) The Ubiquitin-Editing Enzyme A20 (TNFAIP3) Is a Central Regulator of Immunopathology. Trends in Immunology, 30, 383-391. [Google Scholar] [CrossRef] [PubMed]
[48] Fu, B., Lin, X., Tan, S., et al. (2021) MiR-342 Controls Mycobacterium tuberculosis Susceptibility by Modulating Inflammation and Cell Death. EMBO Reports, 22, e52252. [Google Scholar] [CrossRef] [PubMed]
[49] Xi, X., Zhang, C., Han, W., et al. (2015) MicroRNA-223 Is Up-regulated in Active Tuberculosis Patients and Inhibits Apoptosis of Macrophages by Targeting FOXO3. Genetic Testing and Molecular Biomarkers, 19, 650-656. [Google Scholar] [CrossRef] [PubMed]
[50] Tripathi, A., Srivastava, V. and Singh, B.N. (2018) hsa-let-7b-5p Fa-cilitates Mycobacterium tuberculosis Survival in THP-1 Human Macrophages by Fas Downregulation. FEMS Microbi-ology Letters, 365, fny040. [Google Scholar] [CrossRef] [PubMed]
[51] Zhang, D., Yi, Z. and Fu, Y. (2019) Downregulation of miR-20b-5p Facilitates Mycobacterium tuberculosis Survival in RAW 264.7 Macrophages via Attenuating the Cell Apoptosis by Mcl-1 Upregulation. Journal of Cellular Biochemistry, 120, 5889-5896. [Google Scholar] [CrossRef] [PubMed]
[52] Liang, S., Song, Z., Wu, Y., et al. (2018) MicroRNA-27b Modulates In-flammatory Response and Apoptosis during Mycobacterium tuberculosis Infection. The Journal of Immunology, 200, 3506-3518. [Google Scholar] [CrossRef] [PubMed]
[53] Liu, G., Wan, Q., Li, J., et al. (2020) Silencing miR-125b-5p At-tenuates Inflammatory Response and Apoptosis Inhibition in Mycobacterium tuberculosis-Infected Human Macrophages by Targeting DNA Damage-Regulated Autophagy Modulator 2 (DRAM2). Cell Cycle, 19, 3182-3194. [Google Scholar] [CrossRef] [PubMed]
[54] Wu, Y., Guo, Z., Yao, K., et al. (2016) The Transcriptional Foundations of Sp110-Mediated Macrophage (RAW264.7) Resistance to Mycobacterium tuberculosis H37Ra. Scientific Reports, 6, Article No. 22041. [Google Scholar] [CrossRef] [PubMed]
[55] Zhang, G., Liu, X., Wang, W., et al. (2016) Down-Regulation of miR-20a-5p Triggers Cell Apoptosis to Facilitate Mycobacterial Clearance through Targeting JNK2 in Human Macro-phages. Cell Cycle, 15, 2527-2538. [Google Scholar] [CrossRef] [PubMed]
[56] Liao, X., Sharma, N., Kapadia, F., et al. (2011) Krüppel-Like Factor 4 Regulates Macrophage Polarization. Journal of Clinical Investigation, 121, 2736-2749. [Google Scholar] [CrossRef] 
[57] Date, D., Das, R., Narla, G., et al. (2014) Kruppel-Like Transcription Factor 6 Regulates Inflammatory Macrophage Polarization. Journal of Biological Chemistry, 289, 10318-10329. [Google Scholar] [CrossRef] 
[58] Sahu, S.K., Kumar, M., Chakraborty, S., et al. (2017) MicroRNA 26a (miR-26a)/KLF4 and CREB-C/EBP β Regulate Innate Immune Signaling, the Polarization of Macrophages and the Trafficking of Mycobacterium tuberculosis to Lysosomes during Infection. PLOS Pathogens, 13, e1006410. [Google Scholar] [CrossRef] [PubMed]
[59] Bi, J., Zeng, X., Zhao, L., et al. (2022) Retraction Notice to: MiR-181a Induces Macrophage Polarized to M2 Phenotype and Promotes M2 Macrophage-Mediated Tumor Cell Me-tastasis by Targeting KLF6 and C/EBPα. Nucleic Acids—Molecular Therapy, 28, 792. [Google Scholar] [CrossRef] [PubMed]
[60] Ahluwalia, P.K., Pandey, R.K., Sehajpal, P.K., et al. (2017) Per-turbed microRNA Expression by Mycobacterium tuberculosis Promotes Macrophage Polarization Leading to Pro-Survival Foam Cell. Frontiers in Immunology, 8, Article No. 107. [Google Scholar] [CrossRef] [PubMed]
[61] Zhao, S., Mi, Y., Guan, B., et al. (2020) Tumor-Derived Exosomal miR-934 Induces Macrophage M2 Polarization to Promote Liver Metastasis of Colorectal Cancer. Journal of Hematology & Oncology, 13, Article No. 156. [Google Scholar] [CrossRef] [PubMed]
[62] Zhang, M., Zhou, Z., Wang, J., et al. (2016) MiR-130b Pro-motes Obesity Associated Adipose Tissue Inflammation and Insulin Resistance in Diabetes Mice through Alleviating M2 Macrophage Polarization via Repression of PPAR-γ. Immunology Letters, 180, 1-8. [Google Scholar] [CrossRef] [PubMed]

为你推荐