病毒感染调控巨噬细胞极化分子机制的研究进展
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摘要
固有免疫是机体抵御病原微生物入侵的第一道防线。巨噬细胞(macrophages, Mφ)在机体中分布广泛并具有十分活跃的生物学功能,在宿主抗病毒固有免疫应答过程中发挥重要作用。既往研究集中于Mφ的吞噬功能及抗原提呈作用,而近年来研究发现,不同活化模式的Mφ对病毒感染后机体的炎症反应具有双重调控作用,Mφ的极化状态与病毒感染性疾病的发生和转归关系密切。病毒感染急性期,Mφ向M1方向极化,M1型Mφ可促进炎症反应,辅助机体清除病原体,但其过度活化可引起细胞因子风暴,加重组织的免疫病理损伤;随着病毒感染相关疾病的进展,Mφ向M2方向极化,M2型Mφ可通过分泌多种抑炎因子发挥免疫调控作用,参与组织修复,亦与感染慢性化密切相关。不同种类的病毒感染机体后可以诱导Mφ向不同方向极化,但其具体调控机制目前尚不清楚。现就Mφ极化在病毒感染过程中的作用及其调控机制作一概述,为相关疾病的发病机制研究奠定理论基础,并为治疗策略的研发提供新的思路。
Innate immunity is the first line of defense against the invasion of pathogenic microorganisms. Macrophages(Mφ), widely distributed in hosts with active biological functions, play an important role in the innate immune responses against viral infection. Previous studies mainly focused on the phagocytic and antigen presenting function of macrophages, while recent researches found that Mφ in different activation modes could modulate the inflammatory responses during viral infection. At the acute stage of viral infection, macrophages turn to M1, facilitate host inflammation and promote pathogen clearance, which would also aggravate tissue immune pathological injury. With the progress of viral infetion associated diseases, macrophages turn to M2, secrete anti-inflammatory cytokines and promote tissue repair, which could lead to chronic viral infection. The polarization mode from macrophages is highly involved with the virus species, while it still remains ambiguous on how the virus infection shape macrophage activation pattern. Here, we summarize the function of macrophage polarization against virus invasion and the involved molecular mechanisms, which would provide a theoretical basis for the pathogenesis and treatment of virus-associated diseases.
Innate immunity is the first line of defense against the invasion of pathogenic microorganisms. Macrophages(Mφ), widely distributed in hosts with active biological functions, play an important role in the innate immune responses against viral infection. Previous studies mainly focused on the phagocytic and antigen presenting function of macrophages, while recent researches found that Mφ in different activation modes could modulate the inflammatory responses during viral infection. At the acute stage of viral infection, macrophages turn to M1, facilitate host inflammation and promote pathogen clearance, which would also aggravate tissue immune pathological injury. With the progress of viral infetion associated diseases, macrophages turn to M2, secrete anti-inflammatory cytokines and promote tissue repair, which could lead to chronic viral infection. The polarization mode from macrophages is highly involved with the virus species, while it still remains ambiguous on how the virus infection shape macrophage activation pattern. Here, we summarize the function of macrophage polarization against virus invasion and the involved molecular mechanisms, which would provide a theoretical basis for the pathogenesis and treatment of virus-associated diseases.
引文
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[26] SUN D, YU Z, FANG X, et al. LncRNA GAS5 inhibits microglial M2 polarization and exacerbates demyelination[J]. EMBO Rep, 2017, 18(10): 1801-1816.
[27] WU X, MENG Y, WANG C, et al. Semaphorin7A aggravates coxsackievirusB3-induced viral myocarditis by increasing alpha1beta1-integrin macrophages and subsequent enhanced inflammatory response[J].J Mol Cell Cardiol, 2018, 114: 48-57.
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[30] SHIREY K A, LAI W, PLETNEVA L M, et al. Role of the lipoxygenase pathway in RSV-induced alternatively activated macrophages leading to resolution of lung pathology[J]. Mucosal Immunol, 2014, 7(3):549-557.
[31] HAJIZADEH M R, MOKARRAM P, KAMALI SARVESTANI E, et al. Recombinant nonstructural 3 protein, rNS3, of hepatitis C virus along with recombinant GP96 induce IL-12, TNFalpha and alpha5 integrin expression in antigen presenting cells[J]. Hepat Mon, 2013, 13(6): e8104-8113.
[32] PRENDERGAST A J, KLENERMAN P, GOULDER P J, et al. The impact of differential antiviral immunity in children and adults[J]. Nat Rev Immunol, 2012, 12(9): 636-648.
[33] HONG J Y, CHUANG Y,STEENROD Q, et al. Macrophage activation state determines the response to rhinovirus infection in a mouse model of allergic asthma[J]. Respir Res, 2014, 15: 63-78.
[34] POGLITSCH M, WEICHHART T, HECKING M, et al. CMV late phase-induced mTOR activation is essential for efficient virus replication in polarized human macrophages[J]. Am J Transplant, 2012, 12(6):1458-1468.
[35] MCGOVERN N, SCHLITZER A, GUNAWAN M, et al. Population of monocyte-derived macrophages[J]. Immunity, 2015, 42(2): 391.
[2] SANTONI G, MORELLI M B, AMANTINI C, et al. "Immuno-transient receptor potential ion channels": The role in monocyte-and macrophage-mediated inflammatory responses[J]. Front Immunol, 2018, 9: 1273.
[3] ATRI C, GUERFALI F Z, LAOUINI D. Role of human macrophage polarization in inflammation during infectious diseases[J]. Int J Mol Sci,2018, 19(6) :e1801-1815.
[4] ZHAO C, QI X, DING M, et al. Pro-inflammatory cytokine dysregulation is associated with novel avian influenza A (H7N9) virus in primary human macrophages[J]. J Gen Virol, 2016, 97(2): 299-305.
[5] CHANNAPPANAVAR R, FEHR A R, VIJAY R, et al. Dysregulated type i interferon and inflammatory monocyte-macrophage responses cause lethal pneumonia in SARS-CoV-infected mice[J]. Cell Host Microbe, 2016, 19(2):181-193.
[6] PEPE G, CALDERAZZI G, DE MAGLIE M, et al. Heterogeneous induction of microglia M2a phenotype by central administration of interleukin-4[J]. J Neuroinflammation, 2014, 11: 211.
[7] MARTINEZ F O, SICA A, MANTOVANI A, et al. Macrophage activation and polarization[J]. Front Biosci, 2008, 13: 453-461.
[8] ARORA S, DEV K, AGARWAL B, et al. Macrophages: their role, activation and polarization in pulmonary diseases[J]. Immunobiology, 2018, 223(4/5): 383-396.
[9] GINHOUX F, JUNG S. Monocytes and macrophages: developmental pathways and tissue homeostasis[J]. Nat Rev Immunol, 2014, 14(6): 392-404.
[10] DOMíNGUEZ-SOTO A, DE LAS CASAS-ENGEL M, BRAGADO R, et al. Intravenous immunoglobulin promotes antitumor responses by modulating macrophage polarization[J]. J Immunol, 2014, 193(10): 5181-5189.
[11] HERBEIN G, VARIN A. The macrophage in HIV-1 infection: from activation to deactivation?[J]. Retrovirology, 2010, 7: 33-.
[12] YANG J, ZHANG L, YU C, et al. Monocyte and macrophage differentiation: circulation inflammatory monocyte as biomarker for inflammatory diseases[J]. Biomark Res, 2014, 2(1):1.
[13] COLE S L, DUNNING J, KOK W L, et al. M1-like monocytes are a major immunological determinant of severity in previously healthy adults with life-threatening influenza[J]. JCI Insight, 2017, 2(7): e91868-91887.
[14] HALSTEAD E S, UMSTEAD T M, DAVIES M L, et al. GM-CSF overexpression after influenza a virus infection prevents mortality and moderates M1-like airway monocyte/macrophage polarization[J]. Respir Res, 2018, 19(1):3-17.
[15] MITEVA K, PAPPRITZ K, EL-SHAFEEY M, et al. Mesenchymal stromal cells modulate monocytes trafficking in coxsackievirus B3-induced myocarditis[J].Stem Cells Transl Med, 2017, 6(4):1249-1261.
[16] CZIMMERER Z, DANIEL B, HORVATH A, et al. The transcription factor STAT6 mediates direct repression of inflammatory enhancers and limits activation of alternatively polarized macrophages[J]. Immunity, 2018, 48(1):75-90.
[17] XU H, ZHU J, SMITH S, et al. Notch-RBP-J signaling regulates the transcription factor IRF8 to promote inflammatory macrophage polarization[J].Nat Immunol, 2012, 13(7): 642-650.
[18] HSU A T, LUPANCU T J, LEE M C, et al. Epigenetic and transcriptional regulation of IL4-induced CCL17 production in human monocytes and murine macrophages[J]. J Biol Chem, 2018, 293(29): 11415-11423.
[19] HAN H S, SHIN J S, LEE S B, et al. Cirsimarin, a flavone glucoside from the aerial part of Cirsium japonicum var. ussuriense (Regel) Kitam. ex Ohwi, suppresses the JAK/STAT and IRF-3 signaling pathway in LPS-stimulated RAW 264.7 macrophages[J]. Chem Biol Interact,2018, 293: 38-47.
[20] SCHNEIDER A,WEIER M,HERDERSCHEE J, et al. IRF5 is a key regulator of macrophage response to lipopolysaccharide in newborns[J].Front Immunol, 2018, 9:1597-1610.
[21] BAER C, SQUADRITO M L, LAOUI D, et al. Suppression of microRNA activity amplifies IFN-gamma-induced macrophage activation and promotes anti-tumour immunity[J]. Nat Cell Biol, 2016, 18(7):790-802.
[22] LI H, JIANG T, LI M Q, et al. Transcriptional regulation of macrophages polarization by microRNAs[J]. Front Immunol,2018, 9:1175-1187.
[23] XUE Z, ZHANG Z, LIU H, et al. LincRNA-Cox2 regulates NLRP3 inflammasome and autophagy mediated neuroinflammation[J]. Cell Death Differ, 2019, 26(1):130-145.
[24] HU G, GONG A Y, WANG Y, et al. LincRNA-Cox2 Promotes late inflammatory gene transcription in macrophages through modulating SWI/SNF-mediated chromatin remodeling[J]. J Immunol, 2016, 196(6): 2799-2808.
[25] Li M, XIE Z, WANG P, et al. The long noncoding RNA GAS5 negatively regulates the adipogenic differentiation of MSCs by modulating the miR-18a/CTGF axis as a ceRNA[J]. Cell Death Dis, 2018, 9(5): 554-567.
[26] SUN D, YU Z, FANG X, et al. LncRNA GAS5 inhibits microglial M2 polarization and exacerbates demyelination[J]. EMBO Rep, 2017, 18(10): 1801-1816.
[27] WU X, MENG Y, WANG C, et al. Semaphorin7A aggravates coxsackievirusB3-induced viral myocarditis by increasing alpha1beta1-integrin macrophages and subsequent enhanced inflammatory response[J].J Mol Cell Cardiol, 2018, 114: 48-57.
[28] NGUYEN T H, MALTBY S, SIMPSON J L, et al. TNF-alpha and macrophages are critical for respiratory syncytial virus-induced exacerbations in a mouse model of allergic airways disease[J]. J Immunol, 2016, 196(9): 3547-3558.
[29] CASSETTA L, KAJASTE-RUDNITSKI A, CORADIN T, et al. M1 polarization of human monocyte-derived macrophages restricts pre and postintegration steps of HIV-1 replication[J]. AIDS, 2013, 27(12): 1847-1856.
[30] SHIREY K A, LAI W, PLETNEVA L M, et al. Role of the lipoxygenase pathway in RSV-induced alternatively activated macrophages leading to resolution of lung pathology[J]. Mucosal Immunol, 2014, 7(3):549-557.
[31] HAJIZADEH M R, MOKARRAM P, KAMALI SARVESTANI E, et al. Recombinant nonstructural 3 protein, rNS3, of hepatitis C virus along with recombinant GP96 induce IL-12, TNFalpha and alpha5 integrin expression in antigen presenting cells[J]. Hepat Mon, 2013, 13(6): e8104-8113.
[32] PRENDERGAST A J, KLENERMAN P, GOULDER P J, et al. The impact of differential antiviral immunity in children and adults[J]. Nat Rev Immunol, 2012, 12(9): 636-648.
[33] HONG J Y, CHUANG Y,STEENROD Q, et al. Macrophage activation state determines the response to rhinovirus infection in a mouse model of allergic asthma[J]. Respir Res, 2014, 15: 63-78.
[34] POGLITSCH M, WEICHHART T, HECKING M, et al. CMV late phase-induced mTOR activation is essential for efficient virus replication in polarized human macrophages[J]. Am J Transplant, 2012, 12(6):1458-1468.
[35] MCGOVERN N, SCHLITZER A, GUNAWAN M, et al. Population of monocyte-derived macrophages[J]. Immunity, 2015, 42(2): 391.