|本期目录/Table of Contents|

[1]林 铃,曹 玮,李太生.IP10 对HIV/AIDS 患者免疫激活作用的研究进展[J].传染病信息,2018,06:505-510.
 LIN Ling,CAO Wei,LI Tai-sheng*.Advances of IP10 on immune activation in HIV/AIDS patients[J].Infectious Disease Information,2018,06:505-510.

IP10 对HIV/AIDS 患者免疫激活作用的研究进展(PDF)




Advances of IP10 on immune activation in HIV/AIDS patients
林 铃曹 玮李太生
100730,中国医学科学院 北京协和医学院 北京协和医院感染内科(林铃、曹玮、李太生)
LIN Ling CAO Wei LI Tai-sheng*
Department of Infectious Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, 100730, China
干扰素-γ 诱导蛋白10免疫激活抗反转录病毒治疗HIV 相关非AIDS 并发症
interferon gamma-induced protein 10 immune activation antiretroviral therapy HIV associated non-AIDS complications
HIV 感染者即使接受了规律有效的抗病毒治疗,其体内仍然存在慢性长期的免疫激活,这已被证明是引起许 多HIV 相关非AIDS 并发症的重要原因。其中固有免疫激活系统产生的趋化因子干扰素-γ 诱导蛋白10(interferon gammainduced protein 10, IP10)近年来在HIV 研究领域受到更多的关注。IP10 是一种由干扰素刺激基因产生的趋化蛋白,在HIV 感染者疾病进展,与HIV 感染者体内的适应性免疫系统相互作用,影响病毒储存库,引起非AIDS 相关并发症方面起到重 要作用。降低IP10 水平或可为HIV 感染者的治疗提供新的思路,为AIDS 的功能性治愈奠定基础。 
Even if HIV-infected patients receive regular and effective antiviral therapy, there is still chronic long-term immune activation in their body, which has been proved to be an important cause of many HIV associated non-AIDS complications. Interferon gamma-induced protein 10 (IP10), which is produced by the innate immune activation system, has attracted more attention in the field of HIV research in recent years. IP10 is a chemotactic protein produced by interferon-stimulated genes and plays an important role in HIV-infected disease progression, interaction with adaptive immune systems in HIV-infected individuals, affecting viral reservoirs and causing HIV associated non-AIDS complications. Reducing the level of IP10 may provide new ideas for the treatment of HIV-infected patients and lay the foundation for functional cure of AIDS.     


[1] 李太生.国内外艾滋病抗病毒治疗研究进展[J]. 传染病信息, 2008,21(6):324-326.
[2] Brown TT, Tassiopoulos K, Bosch RJ, et al. Association between systemic inflammation and incident diabetes in HIV-Infected patients after initiation of antiretroviral therapy[J]. Diabetes Care, 2010, 33(10):2244-2249.
[3] Duprez DA, Neuhaus J, Kuller LH, et al. Inflammation, coagulation and cardio-vascular disease in HIV-infected individuals[J]. PLoS One, 2012, 7:e44454.
[4] Breen EC, Hussain SK, Magpantay L, et al. B-cell stimulatory cytokines and markers of immune activation are elevated several years prior to the diagnosis of systemic AIDS-associated non- Hodgkin B-cell lymphoma[J]. Cancer Epidemiol Biomarkers Prev, 2011, 20(7):1303-1314.
[5] Burdo TH, Weiffenbach A, Woods SP, et al. Elevated sCD163 is a marker of neurocognitive impairment in HIV infection[J]. AIDS, 2013, 27(9):1387-1395.
[6] Lyons JL, Uno H, Ancuta P, et al. Plasma sCD14 is a biomarker associated with impaired neurocognitive test performance in attention and learning domains in HIV infection[J]. J Acquir Immune Defic Syndr, 2011, 57(5):371-379.
[7] Liu M, Guo S, Hibbert JM, et al. CXCL10/IP-10 in infectious diseases pathogenesis and potential therapeutic implications[J]. Cytokine Growth Factor Rev, 2011, 22(3):121-130.
[8] Cervantes-Barragán L, Firner S, Bechmann I, et al. Regulatory T cells selectively preserve immune privilege of self-antigens during viral central nervous system infection[J]. J Immunol, 2012, 188(8):3678-3685.
[9] Baggiolini M, Dewald B, Moser B. Human chemokines: an update [J]. Annu Rev Immunol, 1997, 15:675-705.
[10] Langford SE, Jintanat A, Cooper DA. Predictors of disease progression in HIV infection: a review[J]. AIDS Res Ther, 2007, 4:11.
[11] Juompan LY, Hutchinson K, Montefiori DC, et al. Analysis of the immune responses in chimpanzees infected with HIV type 1 isolates[J]. AIDS Res Hum Retroviruses, 2008, 24(4):573-586.
[12] Jiao Y, Zhang T, Wang R, et al. Plasma IP-10 is associated with rapid disease progression in early HIV-1 infection[J]. Viral Immunol, 2012, 25(4):333-337.
[13] Pastor L, Casellas A, Carrillo J, et al. IP-10 levels as an accurate screening tool to detect acute HIV infection in resource-limited settings[J]. Sci Rep, 2017, 7(1):8104.
[14] Pastor L, Casellas A, Rupérez M, et al. Interferon-γ-inducible protein 10 (IP-10) as a screening tool to optimize human immunodeficiency virus RNA monitoring in resource-limited settings[J]. Clin Infect Dis, 2017, 65(10):1670-1675.
[15] Lane BR, King SR, Bock PJ, et al. The C-X-C chemokine IP-10 stimulates HIV-1 replication[J]. Virology, 2003, 307(1):122- 134.
[16] Cameron PU, Saleh S, Sallmann G, et al. Establishment of HIV- 1 latency in resting CD4+ T cells depends on chemokine-induced changes in the actin cytoskeleton[J]. Proc Natl Acad Sci U S A, 2010, 107(39):16934-16939.
[17] C?rtes, Fernanda H, De Paula, et al. Plasmatic levels of IL-18, IP- 10, and activated CD8+ T cells are potential biomarkers to identify HIV-1 elite controllers with a true functional cure profile[J]. Front Immunol, 2018, 9:1576.
[18] Dugast AS, Arnold K, Lofano G, et al. Virus-driven inflammation is associated with the development of bNAbs in spontaneous controllers of HIV[J]. Clin Infect Dis, 2017, 64(8):1098-1104.
[19] Noel N, Boufassa F, Lécuroux C, et al. Elevated IP10 levels are associated with immune activation and low CD4+ T-cell counts in HIV controller patients[J]. AIDS, 2014, 28(4):467-476.
[20] Noel N, Lerolle N, Camille Lécuroux, et al. Immunologic and virologic progression in HIV controllers: The role of viral “Blips” and Immune Activation in the ANRS CO21 CODEX Study[J]. PloS One, 2015, 10(7):e0131922.
[21] Ramirez LA, Arango TA, Thompson E, et al. High IP-10 levels decrease T cell function in HIV-1-infected individuals on ART[J]. J Leukoc Biol, 2014, 96(6):1055-1063.
[22] Shive CL, Judge CJ, Clagett B. Pre-vaccine plasma levels of soluble inflammatory indices negatively predict responses to HAV, HBV, and tetanus vaccines in HCV and HIV infection[J]. Vaccine, 2017, 36(4):453-460. 图1 IP10 在HIV 感染中的作用 Figure 1 Role of IP10 in HIV infection 传染病信息 2018 年12 月30 日 第31 卷 第6 ·510· 期 Infect Dis Info, Vol. 31, No. 6, December 30, 2018
[23] Liovat AS, Rey-Cuillé MA, Lécuroux C, et al. Acute plasma biomarkers of T cell activation set-point levels and of disease progression in HIV-1 infection[J]. PLoS One, 2012, 7(10):e46143.
[24] Rodger AJ . Activation and coagulation biomarkers are independent predictors of the development of opportunistic disease in patients with HIV infection[J]. J Infect Dis, 2009, 200(6):973-983.
[25] Peltenburg NC, Schoeman JC, Hou J, et al. Persistent metabolic changes in HIV-infected patients during the first year of combination antiretroviral therapy[J]. Sci Rep, 2018, 8(1):16947.
[26] Pastor L, Urrea V, Carrillo J, et al. Dynamics of CD4 and CD8 T-Cell subsets and inflammatory biomarkers during early and chronic HIV infection in Mozambican adults[J]. Front Immunol, 2018, 8:1925.
[27] Bacchus C, Cheret A, Avettand-Feno?l V, et al. A single HIV-1 cluster and a skewed immune homeostasis drive the early spread of HIV among resting CD4+ cell subsets within one month postinfection [J]. PLoS One, 2013, 8(5):e64219.
[28] Hollingsworth TD, Anderson RM, Fraser C. HIV-1 transmission, by stage of infection[J]. J Infect Dis, 2008, 198(5):687-693.
[29] Hatano H, Jain V, Hunt PW, et al. Cell-based measures of viral persistence are associated with immune activation and programmed cell death protein 1 (PD-1)-expressing CD4+ T cells[J]. J Infect Dis, 2013, 208(1):50-56.
[30] Weiss L, Chevalier MF, Assoumou L, et al. T-cell activation positively correlates with cell-associated HIV-DNA level in viremic patients with primary or chronic HIV-1 infection[J]. AIDS, 2014, 28(11):1683-1687.
[31] Gosselin A, Monteiro P, Chomont N, et al. Peripheral blood CCR4+CCR6+ and CXCR3+CCR6+CD4+ T cells are highly permissive to HIV-1 infection[J]. J Immunol, 2010, 184(3):1604-1616.
[32] Khoury G, Anderson JL, Fromentin R, et al. Persistence of integrated HIV DNA in CXCR3+CCR6+memory CD4+ T cells in HIV-infected individuals on antiretroviral therapy[J]. AIDS, 2016, 30(10):1511-1520.
[33] Foley JF, Yu CR, Solow R, et al. Roles for CXC chemokine ligands 10 and 11 in recruiting CD4+ T cells to HIV-1-infected monocytederived macrophages, dendritic cells, and lymph nodes[J]. J Immunol, 2005, 174(8):4892-4900.
[34] Ploquin MJ, Madec Y, Casrouge A, et al. Elevated basal preinfection CXCL10 in plasma and in the small intestine after infection are associated with more rapid HIV/SIV disease onse[t J]. PLoS Pathog, 2016, 12(8):e1005774.
[35] Chéret A, Durier C, Mélard A, et al. Impact of early cART on HIV blood and semen compartments at the time of primary infection[J]. PLoS One, 2017, 12(7):e0180191.
[36] Ghosn J, Viard JP, Katlama C, et al. Evidence of genotypic resistance diversity of archived and circulating viral strains in blood and semen of pre-treated HIV-infected men[J]. AIDS, 2004, 18(3):447-457.
[37] Kawamura A, Miura S, Fujino M, et al. CXCR3 chemokine receptor-plasma IP10 interaction in patients with coronary artery disease[J]. Circ J, 2003, 67(10):851-854.
[38] Stiksrud B, Lorvik KB, Kvale D, et al. Plasma IP-10 is increased in immunological nonresponders and associated with activated regulatory T cells and persisting low CD4 counts[J]. J Acquir Immune Defic Syndr, 2016, 73(2):138-148.
[39] Heller EA, Liu E, Tager AM, et al. Chemokine CXCL10 promotes atherogenesis by modulating the local balance of effector and regulatory T cells[J]. Circulation, 2006, 113(19):2301-2312.
[40] Brites-Alves C, Luz E, Netto EM, et al. Immune activation, proinflammatory cytokines, and conventional risks for cardiovascular disease in HIV patients: a case-control study in Bahia, Brazil[J]. Front Immunol, 2018, 9:1469.
[41] Mascia C, Lichtner M, Zuccalà P, et al. Active HCV infection is associated with increased circulating levels of interferongamma (IFN-γ)-inducible protein-10 (IP-10), soluble CD163 and inflammatory monocytes regardless of liver fibrosis and HIV coinfection[J]. Clin Res Hepatol Gastroenterol, 2017, 41(6):644-655.
[42] Agrawal R, Balne PK, Veerappan A, et al. A distinct cytokines profile in tear film of dry eye disease (DED) patients with HIV infection[J]. Cytokine, 2016, 88:77-84.
[43] de Almeida, Sérgio M, Rotta I, et al. Blood-CSF barrier and compartmentalization of CNS cellular immune response in HIV infection[J]. J Neuroimmunol, 2016, 301:41-48.
[44] González-Scarano F, Martín-García J. The neuropathogenesis of AIDS[J]. Nat Rev Immunol, 2005, 5(1):69-81.
[45] Davis RL, Syapin PJ. Chronic ethanol inhibits CXC chemokine ligand 10 production in human A172 astroglia and astroglialmediated leukocyte chemotaxis[J]. Neurosci Lett, 2004, 362(3):220-225.
[46] van Marle G, Henry S, Todoruk T, et al. Human immunodeficiency virus type 1 Nef protein mediates neural cell death: a neurotoxic role for IP-10[J]. Virology, 2004, 329(2):302-318.
[47] Kolb SA, Sporer B, Lahrtz F, et al. Identification of a T cell chemotactic factor in the cerebrospinal fluid of HIV-1-infected individuals as interferon-γ inducible protein 10[J]. J Neuroimmunol, 1999, 93(1-2):172-181.
[48] Williams R, Yao H, Peng F, et al. Cooperative induction of CXCL10 involves NADPH oxidase: implications for HIV dementia [J]. Glia, 2010, 58(5):611-621.
[49] Zhou F, Liu XM, Zuo DJ, et al. HIV-1 Nef-induced lncRNA AK006025 regulates CXCL9/10/11 cluster gene expression in astrocytes through interaction with CBP/P300[J]. J Neuroinflammation, 2018, 15(1):303.
[50] Williams R, Yao H, Dhillon NK, et al. HIV-1 tat co-operates with IFN-γ and TNF-α to increase CXCL10 in human astrocytes[J]. PLoS One, 2009, 4(5):e5709.
[51] Song HY, Ryu J, Ju SM, et al. Extracellular HIV-1 Tat enhances monocyte adhesion by up-regulation of ICAM-1 and VCAM-1 gene expression via ROS-dependent NF-κB activation in astrocytes[J]. Exp Mol Med, 2007, 39(1):27-37.


[ 基金项目] “十三五”国家科技重大专项(2017ZX10202101); 中国医学科学院医学与健康科技创新工程项目(2017-I2M-1-014)
[ 作者单位] 100730,中国医学科学院 北京协和医学院 北京协和 医院感染内科(林铃、曹玮、李太生)
[ 通信作者] 李太生,E-mail: litsh@263.net
更新日期/Last Update: 2018-12-30