HBV诱导的髓源性抑制细胞亚群及其在慢性HBV感染中的作用

邬志惠; 杨苗苗; 涂正坤

doi:10.3969/j.issn.1001-5256.2019.12.030

HBV诱导的髓源性抑制细胞亚群及其在慢性HBV感染中的作用

DOI: 10.3969/j.issn.1001-5256.2019.12.030

吉林大学第一医院转化医学研究院

基金项目:

国家自然科学基金(81373143,81571535)；

详细信息

中图分类号: R512.62
计量
- 文章访问数: 776
- HTML全文浏览量: 27
- PDF下载量: 214
- 被引次数: 0
出版历程
- 收稿日期: 2019-09-02
- 出版日期: 2019-12-20

Role of hepatitis B virus-induced myeloid-derived suppressor cell subsets in chronic HBV infection

Research Institute of Translational Medicine,The First Hospital of Jilin University

Research funding:

摘要

摘要: HBV是一种嗜肝性DNA病毒,HBV感染不会引起直接的肝细胞病变,宿主免疫应答决定了病毒能否被清除,同时也是导致HBV相关肝脏疾病的主要原因。髓源性抑制细胞(MDSC)是一群起源于骨髓的非淋巴免疫抑制性细胞,多种病理条件下调节固有和获得性免疫应答。研究发现慢性乙型肝炎患者外周血中MDSC明显高于健康人群,主要介绍了HBV诱导的MDSC亚群在HBV持续感染和肝脏病理学机制中的作用。
- 乙型肝炎病毒 /
- 髓源性抑制细胞 /
- 乙型肝炎,慢性 /
- 免疫,细胞 /
- T淋巴细胞
Abstract: Hepatitis B virus( HBV) is a member of hepadnavirus,and HBV infection may not cause direct hepatocyte lesions. Host immune response determines whether the virus can be eliminated and is a major cause of HBV-related liver diseases. Myeloid-derived suppressor cells( MDSCs) are a group of non-lymphoid immune suppressor cells originating from bone marrow and can regulate innate and adaptive immune responses under different pathological conditions. Studies have shown that chronic hepatitis B patients have a significantly higher number of MDSCs in peripheral blood than the healthy population. This article introduces the role of HBV-induced MDSC subsets in persistent HBV infection and liver pathological mechanism.
- hepatitis B virus /
- myeloid-derived suppressor cells /
- hepatitis B,chronic /
- immunity,cellular /
- T-lymphocytes

HTML全文

参考文献(54)

[1] TONG S,REVILL P. Overview of hepatitis B viral replication and genetic variability[J]. J Hepatol,2016,64(1 Suppl):s4-s16.

[2] SEEGER C,MASON WS. Molecular biology of hepatitis B virus infection[J]. Virology,2015,479-480:672-686.

[3] GANEM D,PRINCE AM. Hepatitis B virus infection—natural history and clinical consequences[J]. N Engl J Med,2004,350(11):1118-1129.

[4] PAN CQ,ZHANG JX. Natural history and clinical consequences of hepatitis B virus infection[J]. Int J Med Sci,2005,2(1):36-40.

[5] TR PO C,CHAN H L Y,LOK A. Hepatitis B virus infection[J]. The Lancet,2014,384(9959):2053-2063.

[6] LIANG TJ,BLOCK TM,MCMAHON BJ,et al. Present and future therapies of hepatitis B:From discovery to cure[J]. Hepatology,2015,62(6):1893-1908.

[7] KONDO Y,SHIMOSEGAWA T. Significant roles of regulatory T cells and myeloid derived suppressor cells in hepatitis B virus persistent infection and hepatitis B virus-related HCCs[J].Int J Mol Sci,2015,16(2):3307-3322.

[8] TAMADAHO R,HOERAUF A,LAYLAND LE. Immunomodulatory effects of myeloid-derived suppressor cells in diseases:Role in cancer and infections[J]. Immunobiology,2018,223(4-5):432-442.

[9] BRONTE V,BRANDAU S,CHEN SH,et al. Recommendations for myeloid-derived suppressor cell nomenclature and characterization standards[J]. Nat Commun, 2016, 7:12150.

[10] MILLRUD CR,BERGENFELZ C,LEANDERSSON K. On the origin of myeloid-derived suppressor cells[J]. Oncotarget,2017,8(2):3649-3665.

[11] ZHANG W,HUANG J,WANG M,et al. Characterization of monocytic and granulocytic subsets of myeloid-derived suppressor cells in blood donors with occult hepatitis B virus infection[J]. J Med Virol,2019,91(2):330-335.

[12] FANG Z,LI J,YU X,et al. Polarization of monocytic myeloid-derived suppressor cells by hepatitis B surface antigen Is mediated via ERK/IL-6/STAT3 signaling feedback and restrains the activation of T cells in chronic hepatitis B virus infection[J]. J Immunol,2015,195(10):4873-4883.

[13] YANG F,YU X,ZHOU C,et al. Hepatitis B e antigen induces the expansion of monocytic myeloid-derived suppressor cells to dampen T-cell function in chronic hepatitis B virus infection[J]. PLo S Pathog,2019,15(4):e1007690.

[14] HUANG A,ZHANG B,YAN W,et al. Myeloid-derived suppressor cells regulate immune response in patients with chronic hepatitis B virus infection through PD-1-induced IL-10[J]. J Immunol,2014,193(11):5461-5469.

[15] PAL S,NANDI M,DEY D,et al. Myeloid-derived suppressor cells induce regulatory T cells in chronically HBV infected patients with high levels of hepatitis B surface antigen and persist after antiviral therapy[J]. Aliment Pharmacol Ther,2019,49(10):1346-1359.

[16] ZENG Y,LI Y,XU Z,et al. Myeloid-derived suppressor cells expansion is closely associated with disease severity and progression in HBV-related acute-on-chronic liver failure[J].J Med Virol,2019,91(8):1510-1518.

[17] MAKVANDI M. Update on occult hepatitis B virus infection[J]. World J Gastroenterol,2016,22(39):8720-8734.

[18] LV Y,CUI M,LV Z,et al. Expression and significance of peripheral myeloid-derived suppressor cells in chronic hepatitis B patients[J]. Clin Res Hepatol Gastroenterol,2018,42(5):462-469.

[19] PILLAY J,TAK T,KAMP VM,et al. Immune suppression by neutrophils and granulocytic myeloid-derived suppressor cells:Similarities and differences[J]. Cell Mol Life Sci,2013,70(20):3813-3827.

[20] ZILIO S,SERAFINI P. Neutrophils and granulocytic MDSC:The janus god of cancer immunotherapy[J]. Vaccines(Basel),2016,4(3):31.

[21] RODRIGUEZ PC,ERNSTOFF MS,HERNANDEZ C,et al. Arginase I-producing myeloid-derived suppressor cells in renal cell carcinoma are a subpopulation of activated granulocytes[J]. Cancer Res,2009,69(4):1553-1560.

[22] SAGIV JY,MICHAELI J,ASSI S,et al. Phenotypic diversity and plasticity in circulating neutrophil subpopulations in cancer[J].Cel Rep,2015,10(4):562-573.

[23] NEGOREV D,BEIER UH,ZHANG T,et al. Human neutrophils can mimic myeloid-derived suppressor cells(PMN-MDSC)and suppress microbead or lectin-induced T cell proliferation through artefactual mechanisms[J]. Sci Rep,2018,8(1):3135.

[24] PALLETT LJ,GILL US,QUAGLIA A,et al. Metabolic regulation of hepatitis B immunopathology by myeloid-derived suppressor cells[J]. Nat Med,2015,21(6):591-600.

[25] DANDRI M,BOCKMANN JH. The challenge of protecting without overprotecting:The two sides of myeloid-derived suppressor cells in hepatitis B viral infection[J]. Hepatology,2016,63(3):1043-1046.

[26] HU S,LIU X,GAO Y,et al. Hepatitis B virus inhibits neutrophil extracellular trap release by modulating reactive oxygen species production and autophagy[J]. J Immunol,2019,202(3):805-815.

[27] LEU CM,LU YC,PENG WL,et al. The hepatitis B virus e antigen suppresses the respiratory burst and mobility of human monocytes and neutrophils[J]. Immunobiology,2014,219(11):880-887.

[28] LU LR,LIU J,XU Z,et al. Expression and clinical significance of myeloid derived suppressor cells in chronic hepatitis B patients[J]. Asian Pac J Cancer Prev,2014,15(10):4367-4372.

[29] CHEN S,AKBAR SM,ABE M,et al. Immunosuppressive functions of hepatic myeloid-derived suppressor cells of normal mice and in a murine model of chronic hepatitis B virus[J]. Clin Exp Immunol,2011,166(1):134-142.

[30] HAN Q,HOU Z,YIN C,et al. 5'-triphosphate siRNA targeting HBx elicits a potent anti-HBV immune response in pAAV-HBV transfected mice[J]. Antiviral Res,2019,161:36-45.

[31] YAN H,ZHANG X,LV Y. The effect of entecavir therapy on immune status in chronic hepatitis B patients[J]. Iran J Immunol,2019,16(1):84-91.

[32] KONG X,SUN R,CHEN Y,et al．γδT cells drive myeloidderived suppressor cell-mediated CD8+T cell exhaustion in hepatitis B virus-induced immunotolerance[J]. J Immunol,2014,193(4):1645-1653.

[33] MAINI MK,GEHRING AJ. The role of innate immunity in the immunopathology and treatment of HBV infection[J]. J Hepatol,2016,64(1 Suppl):s60-s70.

[34] LI TY,YANG Y,ZHOU G,et al. Immune suppression in chronic hepatitis B infection associated liver disease:A review[J].World J Gastroenterol,2019,25(27):3527-3537.

[35] XIA Y,PROTZER U. Control of hepatitis B virus by cytokines[J]. Viruses,2017,9(1):E18.

[36] LIU F,DUAN X,WAN Z,et al. Lower number and decreased function of natural killer cells in hepatitis B virus related acuteon-chronic liver failure[J]. Clin Res Hepatol Gastroenterol,2016,40(5):605-613.

[37] LI H,ZHAI N,WANG Z,et al. Regulatory NK cells mediated between immunosuppressive monocytes and dysfunctional T cells in chronic HBV infection[J]. Gut,2018,67(11):2035-2044.

[38] GAO M,HUANG A,SUN Z,et al. Granulocytic myeloid-derived suppressor cell population increases with the severity of alcoholic liver disease[J]. J Cell Mol Med,2019,23(3):2032-2041.

[39] ORTEGA-PRIETO AM,DORNER M. Immune evasion strategies during chronic hepatitis B and C virus infection[J]. Vaccines(Basel),2017,5(3):24.

[40] BENGSCH B,THIMME R. For whom the interferons toll-TLR7mediated boosting of innate and adaptive immunity against chronic HBV infection[J]. J Hepatol,2018,68(5):883-886.

[41] TRAUTMANN T,KOZIK JH,CARAMBIA A,et al. CD4+Tcell help is required for effective CD8+T cell-mediated resolution of acute viral hepatitis in mice[J]. PLo S One,2014,9(1):e86348.

[42] YE B,LIU X,LI X,et al. T-cell exhaustion in chronic hepatitis B infection:Current knowledge and clinical significance[J]. Cell Death Dis,2015,6:e1694.

[43] MUNDER M,SCHNEIDER H,LUCKNER C,et al. Suppression of T-cell functions by human granulocyte arginase[J].Blood,2006,108(5):1627-1634.

[44] MENNDEZ-ARIAS L，LVAREZ M,PACHECO B. Nucleoside/nucleotide analog inhibitors of hepatitis B virus polymerase:Mechanism of action and resistance[J]. Curr Opin Virol,2014,8(10):1-9.

[45] SHI M,SUN WL,HUA YY,et al. Effects of entecavir on hepatitis B virus covalently closed circular DNA in hepatitis B e antigen-positive patients with hepatitis B[J]. PLo S One,2015,10(2):e0117741.

[46] GUIDOTTI LG,CHISARI FV. Immunobiology and pathogenesis of viral hepatitis[J]. Annu Rev Pathol,2006,1:23-61.

[47] PELLICORO A,RAMACHANDRAN P,IREDALE JP,et al. Liver fibrosis and repair:Immune regulation of wound healing in a solid organ[J]. Nat Rev Immunol,2014,14(3):181-194.

[48] BOURBONNAIS E,RAYMOND VA,ETHIER C,et al. Liver fibrosis protects mice from acute hepatocellular injury[J]. Gastroenterology,2012,142(1):130-139. e4.

[49] FRIEDMAN SL. Hepatic stellate cells:Protean,multifunctional,and enigmatic cells of the liver[J]. Physiol Rev,2008,88(1):125-172.

[50] ELWAN N,SALEM ML,KOBTAN A,et al. High numbers of myeloid derived suppressor cells in peripheral blood and ascitic fluid of cirrhotic and HCC patients[J]. Immunol Invest,2018,47(2):169-180.

[51] YOSHIDA K,MURATA M,YAMAGUCHI T,et al. TGF-β/Smad signaling during hepatic fibro-carcinogenesis(review)[J]. Int J Oncol,2014,45(4):1363-1371.

[52] GAO B,RADAEVA S. Natural killer and natural killer T cells in liver fibrosis[J]. Biochim Biophys Acta,2013,1832(7):1061-1069.

[53] LI T,YANG Y,SONG H,et al. Activated NK cells kill hepatic stellate cells via p38/PI3K signaling in a TRAIL-involved degranulation manner[J]. J Leukoc Biol,2019,105(4):695-704.

[54] WENG H,MERTENS PR,GRESSNER AM,et al. IFN-gamma abrogates profibrogenic TGF-beta signaling in liver by targeting expression of inhibitory and receptor Smads[J]. J Hepatol,2007,46(2):295-303.

施引文献

资源附件(0)

访问统计