新城疫病毒通过抑制树突状细胞白介素12的表达抑制抗原递呈

南福龙; 南文龙; 焉鑫; 王惠; 江莎莎; 张树芸; 于忠杰; 张现娟; 刘俸君; 李俊; 周晓琼; 牛德磊; 李一权; 汪伟; 史宁; 金宁一; 解长占; 崔晓妮; 张赫; 王斌; 鲁会军

doi:10.1631/jzus.B2300134

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Research Article | Updated：2024-03-06

新城疫病毒通过抑制树突状细胞白介素12的表达抑制抗原递呈
Newcastle disease virus suppresses antigen presentation via inhibiting IL-12 expression in dendritic cells
浙江大学学报（英文版）（B辑：生物医学和生物技术） 2024年25卷第3期页码：254-270
Affiliations：

1.Department of Special Medicine, Department of Pathogenic Biology, School of Basic Medicine, Qingdao University, Qingdao 266071, China
2.China Animal Health and Epidemiology Center, Qingdao 266032, China
3.Academician Workstation of Jilin Province, Changchun University of Chinese Medicine, Changchun 130117, China
4.Institute of Virology, Wenzhou University, Wenzhou 325035, China
5.College of Veterinary Medicine, Jilin University, Changchun 130012, China
6.Changchun Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Changchun 130122, China
7.Sino-Cell Biomed Co., Ltd., Qingdao 266000, China
Funds：

the Qingdao Postdoctoral Application Research Project(RZ2200001472);the Shandong Provincial Innovative Ability Improvement Project of Scientific and Technological Small and Medium-Size Enterprise(2022TSGC1142);the Shandong Provincial Science and Technology Foundation(2019JZZY011009);the Qingdao Municipal Science and Technology Foundation(20-2-3-4-nsh)
DOI：10.1631/jzus.B2300134
中图分类号：
CSTR：

南福龙,南文龙,焉鑫等.新城疫病毒通过抑制树突状细胞白介素12的表达抑制抗原递呈[J].浙江大学学报（英文版）（B辑：生物医学和生物技术）,2024,25(03):254-270.

Fulong NAN, Wenlong NAN, Xin YAN, et al. Newcastle disease virus suppresses antigen presentation via inhibiting IL-12 expression in dendritic cells[J]. Journal of Zhejiang University-SCIENCE B (Biomedicine & Biotechnology), 2024,25(3):254-270.
南福龙,南文龙,焉鑫等.新城疫病毒通过抑制树突状细胞白介素12的表达抑制抗原递呈[J].浙江大学学报（英文版）（B辑：生物医学和生物技术）,2024,25(03):254-270. DOI： 10.1631/jzus.B2300134.

Fulong NAN, Wenlong NAN, Xin YAN, et al. Newcastle disease virus suppresses antigen presentation via inhibiting IL-12 expression in dendritic cells[J]. Journal of Zhejiang University-SCIENCE B (Biomedicine & Biotechnology), 2024,25(3):254-270. DOI： 10.1631/jzus.B2300134.

摘要

新城疫病毒作为一种极具潜力的疫苗载体，已被应用于多种疫苗的开发，但目前对于该病毒在抗原提呈中免疫调节作用的研究较少。为阐明新城疫病毒感染的树突状细胞与T淋巴细胞相互作用时的关键抑制因子，本研究将新城疫病毒疫苗LaSota株作为抑制剂对树突状细胞进行预处理，并用细菌脂多糖刺激树突状细胞的活化，通过采用酶联免疫吸附法（ELISA）、流式细胞术、免疫印迹和荧光定量聚合酶链式反应（qRT-PCR）检测相关指标的变化。结果表明，新城疫病毒感染通过p38丝裂原活化蛋白激酶（MAPK）依赖的方式抑制树突状细胞中白介素12p40（IL-12p40）亚基的表达，从而抑制IL-12的活性单位IL-12p70的合成，致使树突状细胞诱导的T细胞增殖和γ干扰素（IFN-γ）、肿瘤坏死因子α（TNF-α）和6型白介素（IL-6）分泌下降。同时，细胞因子的下调促进了新城疫病毒从树突状细胞向T淋巴细胞的传播。此外，不同毒力型的新城疫病毒均表现出抑制活性。综上所述，新城疫病毒可以调节多种免疫细胞互作的强度，从而促进病毒的增殖与传播。因此，本研究揭示了一种新城疫病毒的新型免疫抑制机制，同时也为新城疫病毒载体疫苗的改进提供了新的思路。

Abstract

As a potential vectored vaccine, Newcastle disease virus (NDV) has been subject to various studies for vaccine development, while relatively little research has outlined the immunomodulatory effect of the virus in antigen presentation. To elucidate the key inhibitory factor in regulating the interaction of infected dendritic cells (DCs) and T cells, DCs were pretreated with the NDV vaccine strain LaSota as an inhibitor and stimulated with lipopolysaccharide (LPS) for further detection by enzyme-linked immunosorbent assay (ELISA), flow cytometry, immunoblotting, and quantitative real-time polymerase chain reaction (qRT-PCR). The results revealed that NDV infection resulted in the inhibition of interleukin (IL)-12p40 in DCs through a p38 mitogen-activated protein kinase (MAPK)‍-dependent manner, thus inhibiting the synthesis of IL-12p70, leading to the reduction in T cell proliferation and the secretion of interferon-γ (IFN-γ), tumor necrosis factor-α (TNF-α), and IL-6 induced by DCs. Consequently, downregulated cytokines accelerated the infection and viral transmission from DCs to T cells. Furthermore, several other strains of NDV also exhibited inhibitory activity. The current study reveals that NDV can modulate the intensity of the innate‍‒‍adaptive immune cell crosstalk critically toward viral invasion improvement, highlighting a novel mechanism of virus-induced immunosuppression and providing new perspectives on the improvement of NDV-vectored vaccine.

关键词

新城疫病毒树突状细胞白介素12T淋巴细胞免疫抑制

Keywords

Newcastle disease virusDendritic cellsInterleukin-12 (IL-12)T cellsImmunosuppression

references

Ayasoufi K, Pfaller CK, 2020. Seek and hide: the manipulating interplay of measles virus with the innate immune system. Curr Opin Virol, 41:18-30. https://doi.org/10.1016/j.coviro.2020.03.001https://doi.org/10.1016/j.coviro.2020.03.001

Baratin M, Foray C, Demaria O, et al., 2015. Homeostatic NF‍-‍κB signaling in steady-state migratory dendritic cells regulates immune homeostasis and tolerance. Immunity, 42(4):627-639. https://doi.org/10.1016/j.immuni.2015.03.003https://doi.org/10.1016/j.immuni.2015.03.003

Brady MT, MacDonald AJ, Rowan AG, et al., 2003. Hepatitis C virus non-structural protein 4 suppresses Th1 responses by stimulating IL-10 production from monocytes. Eur J Immunol, 33(12):3448-3457. https://doi.org/10.1002/eji.200324251https://doi.org/10.1002/eji.200324251

Cardone M, Ikeda KN, Varano B, et al., 2015. HIV-1-induced impairment of dendritic cell cross talk with γδ T lymphocytes. J Virol, 89(9):4798-4808. https://doi.org/10.1128/JVI.03681-14https://doi.org/10.1128/JVI.03681-14

Chen DJ, Liu XW, Xu SK, et al., 2019. TNF‍-‍α induced by porcine reproductive and respiratory syndrome virus inhibits the replication of classical swine fever virus C-strain. Vet Microbiol, 234:25-33. https://doi.org/10.1016/j.vetmic.2019.05.007https://doi.org/10.1016/j.vetmic.2019.05.007

Coughlin MM, Bellini WJ, Rota PA, 2013. Contribution of dendritic cells to measles virus induced immunosuppression. Rev Med Virol, 23(2):126-138. https://doi.org/10.1002/rmv.1735https://doi.org/10.1002/rmv.1735

de Witte L, de Vries RD, van der Vlist M, et al., 2008. DC-SIGN and CD150 have distinct roles in transmission of measles virus from dendritic cells to T-lymphocytes. PLoS Pathog, 4(4):e1000049. https://doi.org/10.1371/journal.ppat.1000049https://doi.org/10.1371/journal.ppat.1000049

Dienz O, Rud JG, Eaton SM, et al., 2012. Essential role of IL-6 in protection against H1N1 influenza virus by promoting neutrophil survival in the lung. Mucosal Immunol, 5(3):258-266. https://doi.org/10.1038/mi.2012.2https://doi.org/10.1038/mi.2012.2

Durai V, Murphy KM, 2016. Functions of murine dendritic cells. Immunity, 45(4):719-736. https://doi.org/10.1016/j.immuni.2016.10.010https://doi.org/10.1016/j.immuni.2016.10.010

Gao HW, Liu X, Sun W, et al., 2017. Total tanshinones exhibits anti-inflammatory effects through blocking TLR4 dimerization via the MyD88 pathway. Cell Death Dis, 8(8):e3004. https://doi.org/10.1038/cddis.2017.389https://doi.org/10.1038/cddis.2017.389

Gately MK, Desai BB, Wolitzky AG, et al., 1991. Regulation of human lymphocyte proliferation by a heterodimeric cytokine, IL-12 (cytotoxic lymphocyte maturation factor). J Immunol, 147(3):874-882. https://doi.org/10.4049/jimmunol.147.3.874https://doi.org/10.4049/jimmunol.147.3.874

Ghilas S, Ambrosini M, Cancel JC, et al., 2021. Natural killer cells and dendritic epidermal γδ T cells orchestrate type 1 conventional DC spatiotemporal repositioning toward CD8+ T cells. iScience, 24(9):103059-103083. https://doi.org/10.1016/j.isci.2021.103059https://doi.org/10.1016/j.isci.2021.103059

Gupta M, Lo MK, Spiropoulou CF, 2013. Activation and cell death in human dendritic cells infected with Nipah virus. Virology, 441(1):49-56. https://doi.org/10.1016/j.virol.2013.03.004https://doi.org/10.1016/j.virol.2013.03.004

Hilligan KL, Ronchese F, 2020. Antigen presentation by dendritic cells and their instruction of CD4+ T helper cell responses. Cell Mol Immunol, 17(6):587-599. https://doi.org/10.1038/s41423-020-0465-0https://doi.org/10.1038/s41423-020-0465-0

Jiang KF, Guo S, Yang C, et al., 2018. Barbaloin protects against lipopolysaccharide (LPS)-induced acute lung injury by inhibiting the ROS-mediated PI3K/AKT/NF-‍κB pathway. Int Immunopharmacol, 64:140-150. https://doi.org/10.1016/j.intimp.2018.08.02https://doi.org/10.1016/j.intimp.2018.08.02

Kürten CHL, Deuß E, Lei YL, et al., 2020. Stimulierende und inhibierende Signalwege der APZ- und T-Zell-Interaktion sowie Einfluss von TLR-Agonisten auf APZ. HNO, 68(12):916-921 (in German). https://doi.org/10.1007/s00106-020-00960-8https://doi.org/10.1007/s00106-020-00960-8

Li YC, Wu QX, Huang LL, et al., 2018. An alternative pathway of enteric PEDV dissemination from nasal cavity to intestinal mucosa in swine. Nat Commun, 9:3811. https://doi.org/10.1038/s41467-018-06056-whttps://doi.org/10.1038/s41467-018-06056-w

Menon MB, Gropengießer J, Fischer J, et al., 2017. P38MAPK/MK2-dependent phosphorylation controls cytotoxic RIPK1 signalling in inflammation and infection. Nat Cell Biol, 19(10):1248-1259. https://doi.org/10.1038/ncb3614https://doi.org/10.1038/ncb3614

Nan FL, Zhang H, Nan WL, et al., 2021a. Lentogenic NDV V protein inhibits IFN responses and represses cell apoptosis. Vet Microbiol, 261:109181. https://doi.org/10.1016/j.vetmic.2021.109181https://doi.org/10.1016/j.vetmic.2021.109181

Nan FL, Zheng W, Nan WL, et al., 2021b. Newcastle disease virus inhibits the proliferation of T cells induced by dendritic cells in vitro and in vivo. Front Immunol, 11:619829. https://doi.org/10.3389/fimmu.2020.619829https://doi.org/10.3389/fimmu.2020.619829

Nie Y, Wang Z, Chai G, et al., 2019. Dehydrocostus lactone suppresses LPS-induced acute lung injury and macrophage activation through NF‍-‍κB signaling pathway mediated by p38 MAPK and Akt. Molecules, 24(8):1510. https://doi.org/10.3390/molecules24081510https://doi.org/10.3390/molecules24081510

Park JG, Oladunni FS, Rohaim MA, et al., 2021. Immunogenicity and protective efficacy of an intranasal live-attenuated vaccine against SARS-CoV-2. iScience, 24(9):102941. https://doi.org/10.1016/j.isci.2021.102941https://doi.org/10.1016/j.isci.2021.102941

Pulendran B, 2015. The varieties of immunological experience: of pathogens, stress, and dendritic cells. Annu Rev Immunol, 33:563-606. https://doi.org/10.1146/annurev-immunol-020711-075049https://doi.org/10.1146/annurev-immunol-020711-075049

Qian G, Li YW, Ma H, et al., 2018. Peiminine protects against lipopolysaccharide-induced mastitis by inhibiting the AKT/NF-κB, ERK1/2 and p38 signaling pathways. Int J Mol Sci, 19(9):2637. https://doi.org/10.3390/ijms19092637https://doi.org/10.3390/ijms19092637

Qiu X, Fu Q, Meng C, et al., 2016. Newcastle disease virus V protein targets phosphorylated STAT1 to block IFN-I signaling. PLoS ONE, 11(2):e0148560. https://doi.org/10.1371/journal.pone.0148560https://doi.org/10.1371/journal.pone.0148560

Rajmani RS, Gupta SK, Singh PK, et al., 2016. HN protein of Newcastle disease virus sensitizes HeLa cells to TNF-‍αinduced apoptosis by downregulating NF‍-‍κB expression. Arch Virol, 161(9):2395-2405. https://doi.org/10.1007/s00705-016-2923-7https://doi.org/10.1007/s00705-016-2923-7

Rescigno M, 2002. Dendritic cells and the complexity of microbial infection. Trends Microbiol, 10(9):425-431. https://doi.org/10.1016/s0966-842x(02)02425-3https://doi.org/10.1016/s0966-842x(02)02425-3

Romanets-Korbut O, Kovalevska LM, Seya T, et al., 2016. Measles virus hemagglutinin triggers intracellular signaling in CD150-expressing dendritic cells and inhibits immune response. Cell Mol Immunol, 13(6):828-838. https://doi.org/10.1038/cmi.2015.55https://doi.org/10.1038/cmi.2015.55

Ronet C, Hauyon-La Torre Y, Revaz-Breton M, et al., 2010. Regulatory B cells shape the development of Th2 immune responses in BALB/c mice infected with Leishmania major through IL-10 production. J Immunol, 184(2):886-894. https://doi.org/10.4049/jimmunol.0901114https://doi.org/10.4049/jimmunol.0901114

Schönrich G, Raftery MJ, 2015. Dendritic cells as Achilles’ heel and Trojan horse during varicella zoster virus infection. Front Microbiol, 6:417. https://doi.org/10.3389/fmicb.2015.00417https://doi.org/10.3389/fmicb.2015.00417

Schulz O, Edwards AD, Schito M, et al., 2000. CD40 triggering of heterodimeric IL-12 p70 production by dendritic cells in vivo requires a microbial priming signal. Immunity, 13(4):453-462. https://doi.org/10.1016/s1074-7613(00)00045-5https://doi.org/10.1016/s1074-7613(00)00045-5

Shrestha B, You DH, Saravia J, et al., 2017. IL-4Rα on dendritic cells in neonates and Th2 immunopathology in respiratory syncytial virus infection. J Leukoc Biol, 102(1):153-161. https://doi.org/10.1189/jlb.4A1216-536Rhttps://doi.org/10.1189/jlb.4A1216-536R

Sun WN, Liu YH, Amanat F, et al., 2021. A Newcastle disease virus expressing a stabilized spike protein of SARS-CoV-2 induces protective immune responses. Nat Commun, 12:6197. https://doi.org/10.1038/s41467-021-26499-yhttps://doi.org/10.1038/s41467-021-26499-y

Sun YJ, Zheng H, Yu SQ, et al., 2019. Newcastle disease virus V protein degrades mitochondrial antiviral signaling protein to inhibit host type I interferon production via E3 ubiquitin ligase RNF5. J Virol, 93(18):e00322-19. https://doi.org/10.1128/jvi.00322-19https://doi.org/10.1128/jvi.00322-19

Tan L, Zhang YQ, Qiao CT, et al., 2018. NDV entry into dendritic cells through macropinocytosis and suppression of T lymphocyte proliferation. Virology, 518:126-135. https://doi.org/10.1016/j.virol.2018.02.011https://doi.org/10.1016/j.virol.2018.02.011

van Panhuys N, 2016. TCR signal strength alters T-DC activation and interaction times and directs the outcome of differentiation. Front Immunol, 7:6. https://doi.org/10.3389/fimmu.2016.00006https://doi.org/10.3389/fimmu.2016.00006

Wonderlich ER, Wu WC, Normolle DP, et al., 2015. Macrophages and myeloid dendritic cells lose T cell-stimulating function in simian immunodeficiency virus infection associated with diminished IL-12 and IFN-α production. J Immunol, 195(7):3284-3292. https://doi.org/10.4049/jimmunol.1500683https://doi.org/10.4049/jimmunol.1500683

Yang X, Arslan M, Liu XJ, et al., 2020. IFN-γ establishes interferon-stimulated gene-mediated antiviral state against Newcastle disease virus in chicken fibroblasts. Acta Biochim Biophys Sin, 52(3):268-280. https://doi.org/10.1093/abbs/gmz158https://doi.org/10.1093/abbs/gmz158

Yoshimura S, Bondeson J, Foxwell BMJ, et al., 2001. Effective antigen presentation by dendritic cells is NF‍-‍κB dependent: coordinate regulation of MHC, co-stimulatory molecules and cytokines. Int Immunol, 13(5):675-683. https://doi.org/10.1093/intimm/13.5.675https://doi.org/10.1093/intimm/13.5.675

Zhang H, Nan FL, Li ZX, et al., 2019. Construction and immunological evaluation of recombinant Newcastle disease virus vaccines expressing highly pathogenic porcine reproductive and respiratory syndrome virus GP3/GP5 proteins in pigs. Vet Microbiol, 239:108490. https://doi.org/10.1016/j.vetmic.2019.108490https://doi.org/10.1016/j.vetmic.2019.108490

Zhang HL, Chen S, Zeng MC, et al., 2018. Apelin-13 administration protects against LPS-induced acute lung injury by inhibiting NF-κB pathway and NLRP3 inflammasome activation. Cell Physiol Biochem, 49(5):1918-1932. https://doi.org/10.1159/000493653https://doi.org/10.1159/000493653

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