白细胞介素-10对口蹄疫病毒感染小鼠T细胞增殖及其表达TNF-α、IFN-γ和IL-2的影响

doi:10.11843/j.issn.0366-6964.2023.02.026

畜牧兽医学报 ›› 2023, Vol. 54 ›› Issue (2): 694-705.doi: 10.11843/j.issn.0366-6964.2023.02.026

白细胞介素-10对口蹄疫病毒感染小鼠T细胞增殖及其表达TNF-α、IFN-γ和IL-2的影响

郭紫晶^1,2, 陈飞², 张志雄², 柏玲^1,2, 张志东^1*, 李彦敏^1*

1. 西南民族大学畜牧兽医学院, 成都 610041;
2. 中国农业科学院兰州兽医研究所家畜疫病病原生物学国家重点实验室OIE/国家口蹄疫参考实验室, 兰州 730046

收稿日期:2022-04-07 出版日期:2023-02-23 发布日期:2023-02-21
通讯作者: 张志东,主要从事动物病毒病致病机制研究,E-mail:zhangzhidong@swun.edu.cn;李彦敏,主要从事动物病毒病免疫机制与防控技术研究,E-mail:liyanmin@swun.edu.cn
作者简介:郭紫晶(1992-),女,布依族,贵州安顺人,博士,主要从事动物病毒病致病机制研究,E-mail:657694728@qq.com
基金资助:
西南民族大学中央高校基本科研业务费专项（2021115）；西南民族大学引进高层次人才科研资助金项目（RQD202100）；四川省自然科学基金（2022NSFSC0073）

Effects of Interleukin-10 on T Cell Proliferation and Its Expression of TNF-α, IFN-γ and IL-2 in Mice Infected with Foot-and-Mouth Disease Virus

GUO Zijing^1,2, CHEN Fei², ZHANG Zhixiong², BAI Ling^1,2, ZHANG Zhidong^1*, LI Yanmin^1*

1. College of Animal Husbandry and Veterinary Medicine, Southwest Minzu University, Chengdu 610041, China;
2. OIE/National Foot and Mouth Disease Reference Laboratory, State Key Laboratory of Veterinary Etiological Biology, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou 730046, China

Received:2022-04-07 Online:2023-02-23 Published:2023-02-21

摘要/Abstract

摘要： 白细胞介素-10（IL-10）增高是口蹄疫病毒（FMDV）感染过程中显著特征之一。本研究旨在探讨IL-10对FMDV感染小鼠外周血T细胞增殖及其表达效应功能相关细胞因子的影响。采用CCK-8和流式细胞术分别检测小鼠外周血T细胞增殖和T细胞表达效应功能相关细胞因子（TNF-α、IFN-γ和IL-2）。结果显示，与对照小鼠相比，FMDV感染小鼠（感染12、24、36和48 h）外周血T细胞对刀豆蛋白A刺激的增殖均显著下降（P<0.05或P<0.01）；FMDV感染小鼠的外周血CD4⁺T细胞表达TNF-α和IL-2均显著下降（均P<0.01），CD8⁺T细胞表达TNF-α、IFN-γ和IL-2也显著下降（P<0.01或P<0.000 1）。体内阻断IL-10/IL-10R信号或者敲除IL-10均能显著恢复FMDV感染小鼠外周血T细胞的增殖（P<0.05或P<0.01），但不影响CD4⁺和CD8⁺T细胞表达TNF-α、IFN-γ和IL-2。本研究首次揭示FMDV能抑制小鼠外周血T细胞增殖及其表达TNF-α、IFN-γ和IL-2，其有助于FMDV逃避宿主免疫反应。尽管体内阻断IL-10/IL-10R信号或者敲除IL-10不影响CD4⁺和CD8⁺T细胞的表达TNF-α、IFN-γ和IL-2，但其有助于恢复外周血T细胞的增殖能力，该结果为FMD新型防控产品的研发提供新的思路。

关键词: 口蹄疫病毒, 白细胞介素-10, T细胞, 细胞增殖, 细胞因子

Abstract: The increase of interleukin-10 (IL-10) is one of the hallmarks during foot-and-mouth disease virus (FMDV) infection. The aim of this study was to investigate the effects of IL-10 on the proliferation and the expressions of function-related cytokines of T cells in peripheral blood of mice infected with FMDV. The proliferation and the expressions of effector function-related cytokines (TNF-α, IFN-γ and IL-2) of T cells in peripheral blood of mice were detected by CCK-8 and flow cytometry, respectively. The results showed that the proliferations of T cells in peripheral blood of FMDV-infected mice at 12, 24, 36 and 48 hpi were significantly decreased compared with that of mock-mice (P<0.05 or P<0.01); and the expressions of TNF-α and IL-2 of CD4⁺ T cells in peripheral blood of infected mice were significantly decreased compared with that of mock-mice (all P<0.01); and the expressions of TNF-α, IFN-γ and IL-2 of CD8⁺ T cells in peripheral blood of infected mice were also significantly decreased compared with that of mock-mice (P<0.01 or P<0.000 1). However, blocking IL-10/IL-10R signaling in vivo or knocking out IL-10 contributed to restore the proliferation of T cells in peripheral blood following FMDV infection (P<0.05 or P<0.01), but did not affect the expressions of TNF-α, IFN-γ and IL-2 of CD4⁺ and CD8⁺ T cells. The study for the first time revealed that the proliferation and the expressions of TNF-α, IFN-γ and IL-2 of T cells were inhibited after FMDV infection, which contributed to evade immune responses. Although blocking IL-10/IL-10R signaling in vivo or knocking out IL-10 did not affect the expressions of TNF-α, IFN-γ and IL-2 of CD4⁺ and CD8⁺ T cells, it contributed to restore the proliferation of T cells in peripheral blood of FMDV-infected mice, providing new perspectives and new strategies for the design of new products for FMD prevention and control.

Key words: foot-and-mouth disease virus, interleukin-10, T cells, proliferation, cytokine

中图分类号:

S852.659.6

郭紫晶, 陈飞, 张志雄, 柏玲, 张志东, 李彦敏. 白细胞介素-10对口蹄疫病毒感染小鼠T细胞增殖及其表达TNF-α、IFN-γ和IL-2的影响[J]. 畜牧兽医学报, 2023, 54(2): 694-705.

GUO Zijing, CHEN Fei, ZHANG Zhixiong, BAI Ling, ZHANG Zhidong, LI Yanmin. Effects of Interleukin-10 on T Cell Proliferation and Its Expression of TNF-α, IFN-γ and IL-2 in Mice Infected with Foot-and-Mouth Disease Virus[J]. Acta Veterinaria et Zootechnica Sinica, 2023, 54(2): 694-705.

参考文献 29

[1]	JAMAL S M, BELSHAM G J. Foot-and-mouth disease:past, present and future[J]. Vet Res, 2013, 44(1):116.
[2]	DOMINGO E, BARANOWSKI E, ESCARMIS C, et al. Foot-and-mouth disease virus[J]. Comp Immunol Microbiol Infect Dis, 2002, 25(5-6):297-308.
[3]	GRUBMAN M J, BAXT B. Foot-and-mouth disease[J]. Clin Microbiol Rev, 2004, 17(2):465-493.
[4]	GRUBMAN M J, MORAES M P, DIAZ-SAN SEGUNDO F, et al. Evading the host immune response:how foot-and-mouth disease virus has become an effective pathogen[J]. FEMS Immunol Med Microbiol, 2008, 53(1):8-17.
[5]	李显, 张富东, 张中旺, 等. 口蹄疫病毒利用自身蛋白逃逸宿主天然免疫应答的研究进展[J]. 畜牧兽医学报, 2020, 51(11):2622-2632.LI X, ZHANG F D, ZHANG Z W, et al. Recent advance on foot-and-mouth disease virus utilizes self-proteins to evade innate immunity response of host[J]. Acta Veterinaria et Zootechnica Sinica, 2020, 51(11):2622-2632. (in Chinese)
[6]	KENUBIH A. Foot and mouth disease vaccine development and challenges in inducing long-lasting immunity:trends and current perspectives[J]. Vet Med (Auckl), 2021, 12:205-215.
[7]	YANG B, ZHANG X H, ZHANG D J, et al. Molecular mechanisms of immune escape for foot-and-mouth disease virus[J]. Pathogens, 2020, 9(9):729.
[8]	RODRÍGUEZ-HABIBE I, CELIS-GIRALDO C, PATARROYO M E, et al. A comprehensive review of the immunological response against foot-and-mouth disease virus infection and its evasion mechanisms[J]. Vaccines (Basel), 2020, 8(4):764.
[9]	ABUBAKAR M, MANZOOR S, AHMED A. Interplay of foot and mouth disease virus with cell-mediated and humoral immunity of host[J]. Rev Med Virol, 2018, 28(2):e1966.
[10]	RAD F R, AJDARY S, OMRANIPOUR R, et al. Comparative analysis of CD4+ and CD8+ T cells in tumor tissues, lymph nodes and the peripheral blood from patients with breast cancer[J]. Iran Biomed J, 2015, 19(1):35-44.
[11]	XIAO M L, CHEN X Y, HE R, et al. Differentiation and function of follicular CD8 T cells during human immunodeficiency virus infection[J]. Front Immunol, 2018, 9:1095.
[12]	DIAZ-SAN SEGUNDO F, SALGUERO F J, DE AVILA A, et al. Selective lymphocyte depletion during the early stage of the immune response to foot-and-mouth disease virus infection in swine[J]. J Virol, 2006, 80(5):2369-2379.
[13]	BAUTISTA E M, FERMAN G S, GOLDE W T. Induction of lymphopenia and inhibition of T cell function during acute infection of swine with foot and mouth disease virus (FMDV)[J]. Vet Immunol Immunopathol, 2003, 92(1-2):61-73.
[14]	ROJAS J M, AVIA M, MARTÍN V, et al. IL-10:a multifunctional cytokine in viral infections[J]. J Immunol Res, 2017, 2017:6104054.
[15]	DÍAZ-SAN SEGUNDO F, RODRÍGUEZ-CALVO T, DE AVILA A, et al. Immunosuppression during acute infection with foot-and-mouth disease virus in swine is mediated by IL-10[J]. PLoS One, 2009, 4(5):e5659.
[16]	ZHANG Z D, DOEL C, BASHIRUDDIN J B. Interleukin-10 production at the early stage of infection with foot-and-mouth disease virus related to the likelihood of persistent infection in cattle[J]. Vet Res, 2015, 46:132.
[17]	GUO Z J, ZHAO Y, ZHANG Z D, et al. Interleukin-10-mediated lymphopenia caused by acute infection with foot-and-mouth disease virus in mice[J]. Viruses, 2021, 13(12):2358.
[18]	刘丹华, 郑世民, 刘晓静, 等. 禽网状内皮组织增生病病毒感染对SPF雏鸡血液和局部淋巴组织CD4+/CD8+细胞及相关细胞因子表达的影响[J]. 畜牧兽医学报, 2020, 51(6):1447-1454.LIU D H, ZHENG S M, LIU X J, et al. Effects of avian reticuloendotheliosis virus infection on the CD4+/CD8+ ratio and the expression of related cytokines in SPF chicks[J]. Acta Veterinaria et Zootechnica Sinica, 2020, 51(6):1447-1454. (in Chinese)
[19]	FAN Y, BAI H W, QIAN Y Y, et al. CD4+ T cell immune response to VP1 and VP3 in BK virus infected recipients of renal transplantation[J]. Surg Infect (Larchmt), 2019, 20(3):236-243.
[20]	SHARAN R, SINGH D K, RENGARAJAN J, et al. Characterizing early T cell responses in nonhuman primate model of tuberculosis[J]. Front Immunol, 2021, 12:706723.
[21]	SUN P, ZHANG S M, QIN X D, et al. Foot-and-mouth disease virus capsid protein VP2 activates the cellular EIF2S1-ATF4 pathway and induces autophagy via HSPB1[J]. Autophagy, 2018, 14(2):336-346.
[22]	GIAMARELLOS-BOURBOULIS E J, NETEA M G, ROVINA N, et al. Complex immune dysregulation in COVID-19 patients with severe respiratory failure[J]. Cell Host Microbe, 2020, 27(6):992-1000. e3.
[23]	PALANQUES-PASTOR T, LÓPEZ-BRIZ E, POVEDA ANDRéS J L. Involvement of interleukin 6 in SARS-CoV-2 infection:siltuximab as a therapeutic option against COVID-19[J]. Eur J Hosp Pharm, 2020, 27(5):297-298.
[24]	POL J G, CAUDANA P, PAILLET J, et al. Effects of interleukin-2 in immunostimulation and immunosuppression[J]. J Exp Med, 2020, 217(1):e20191247.
[25]	MEHTA A K, GRACIAS D T, CROFT M. TNF activity and T cells[J]. Cytokine, 2018, 101:14-18.
[26]	BAXTER A G, HODGKIN P D. Activation rules:the two-signal theories of immune activation[J]. Nat Rev Immunol, 2002, 2(6):439-446.
[27]	CHEN L P, FLIES D B. Molecular mechanisms of T cell co-stimulation and co-inhibition[J]. Nat Rev Immunol, 2013, 13(4):227-242.
[28]	TAYLOR A, VERHAGEN J, BLASER K, et al. Mechanisms of immune suppression by interleukin-10 and transforming growth factor-β:the role of T regulatory cells[J]. Immunology, 2006, 117(4):433-442.
[29]	JUBEL J M, BARBATI Z R, BURGER C, et al. The role of PD-1 in acute and chronic infection[J]. Front Immunol, 2020, 11:487.

白细胞介素-10对口蹄疫病毒感染小鼠T细胞增殖及其表达TNF-α、IFN-γ和IL-2的影响

Effects of Interleukin-10 on T Cell Proliferation and Its Expression of TNF-α, IFN-γ and IL-2 in Mice Infected with Foot-and-Mouth Disease Virus

RichHTML

PDF

可视化

摘要/Abstract

引用本文

使用本文

参考文献 29

相关文章 15

编辑推荐

Metrics

本文评价

[1]	张晨俭, 李隐侠, 丁强, 刘伟佳, 王慧利, 何南, 吴家顺, 曹少先. CRISPR/Cas9技术高效制备山羊SOCS2基因编辑胚胎[J]. 畜牧兽医学报, 2024, 55(1): 129-141.
[2]	苗舒, 安济山, 王祚, 肖定福, 兰欣怡, 刘磊, 沈维军, 万发春. 亮氨酸通过PI3K-AKT信号通路促进牛成肌细胞的增殖[J]. 畜牧兽医学报, 2024, 55(1): 142-152.
[3]	张万锋, 赵天枝, 李娇, 尤紫薇, 杨阳, 蔡春波, 高鹏飞, 曹果清, 郭晓红, 李步高. NR2F2基因调控猪PK15细胞增殖和凋亡的研究[J]. 畜牧兽医学报, 2023, 54(8): 3242-3251.
[4]	王婉洁, 陈南珠, 邹惠影, 周心仪, 郝海生, 庞云渭, 朱化彬, 赵学明, 余大为, 杜卫华. 过表达组蛋白甲基转移酶ASH1L对牛卵丘细胞增殖和凋亡的影响[J]. 畜牧兽医学报, 2023, 54(8): 3358-3368.
[5]	张鹏, 王明秀, 敬科民, 彭巍, 田园, 李雨谦, 付长其, 舒适, 钟金城, 蔡欣. FGFs/FGFRs及其介导信号通路基因的异常表达影响犏牛未分化精原细胞增殖活性[J]. 畜牧兽医学报, 2023, 54(7): 2886-2897.
[6]	邢宝瑞, 刘振, 赵海平, 马泽芳, 李勋胜, 周珏, 孙红梅. 鹿茸逆向成骨的研究进展[J]. 畜牧兽医学报, 2023, 54(6): 2231-2240.
[7]	许甜甜, 张彤彤, 王蒙, 王昕. 转录因子Foxq1通过WNT/β-catenin信号通路影响绒山羊毛囊干细胞增殖的研究[J]. 畜牧兽医学报, 2023, 54(6): 2653-2661.
[8]	周广青, 刘晓庆, 史喜绢, 杨大鹏, 袁莉刚, 常惠芸. 口蹄疫病毒抗体SA-ELISA快速检测方法的建立[J]. 畜牧兽医学报, 2023, 54(5): 2020-2029.
[9]	李硕, 张韵, 白满元, 赵瑞翀, 宋河涛, 穆素雨, 滕志东, 董虎, 马娥宁, 孙世琪, 郭慧琛, 尹双辉. 生物矿化的口蹄疫病毒样颗粒疫苗的免疫原性评价[J]. 畜牧兽医学报, 2023, 54(4): 1598-1607.
[10]	任晓丽, 范玉营, 皇甫和平, 刘云, 石冬梅. GSK126对犬乳腺肿瘤细胞上皮间质转化的影响[J]. 畜牧兽医学报, 2023, 54(4): 1721-1729.
[11]	杨光, 徐景, 李新, 胡德宝, 郭益文, 丁向彬, 郭宏, 张林林. 干扰lncbMD对牛骨骼肌卫星细胞增殖分化的影响[J]. 畜牧兽医学报, 2023, 54(3): 1015-1025.
[12]	杨晓伟, 赵自亮, 付雨, 于子肖, 赵永聚. TET1基因对小鼠uNK细胞增殖及IFN-γ、VEGF-C和TGF-β1转录水平的影响[J]. 畜牧兽医学报, 2023, 54(3): 1221-1228.
[13]	孙雯叶, 李建基, 王亨, 董俊升, 李俊, 崔璐莹. 甲硫脑啡肽通过阿片受体促进脂多糖作用下奶牛子宫内膜基质细胞的增殖[J]. 畜牧兽医学报, 2023, 54(3): 1229-1239.
[14]	孙金魁, 许厚强, 石鹏飞, 阮涌. 关岭牛MEF2A基因干扰载体构建及其转染对成肌细胞的影响[J]. 畜牧兽医学报, 2023, 54(2): 584-595.
[15]	马天文, 于跃, 吕良钰, 贾丽娜, 阮红日, 王颢然, 王新宇, 张雨欣, 张建涛, 高利. 白果内酯对IL-1β诱导的ATDC5软骨细胞自噬、增殖和凋亡的影响[J]. 畜牧兽医学报, 2023, 54(2): 837-846.