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Journal of Zhejiang University SCIENCE B 2024 Vol.25 No.3 P.254-270

http://doi.org/10.1631/jzus.B2300134


Newcastle disease virus suppresses antigen presentation via inhibiting IL-12 expression in dendritic cells


Author(s):  Fulong NAN, Wenlong NAN, Xin YAN, Hui WANG, Shasha JIANG, Shuyun ZHANG, Zhongjie YU, Xianjuan ZHANG, Fengjun LIU, Jun LI, Xiaoqiong ZHOU, Delei NIU, Yiquan LI, Wei WANG, Ning SHI, Ningyi JIN, Changzhan XIE, Xiaoni CUI, He ZHANG, Bin WANG, Huijun LU

Affiliation(s):  Department of Special Medicine, Department of Pathogenic Biology, School of Basic Medicine, Qingdao University, Qingdao 266071, China; more

Corresponding email(s):   huijun_lu@126.com, Wangbin532@126.com

Key Words:  Newcastle disease virus, Dendritic cells, Interleukin-12 (IL-12), T cells, Immunosuppression


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Fulong NAN, Wenlong NAN, Xin YAN, Hui WANG, Shasha JIANG, Shuyun ZHANG, Zhongjie YU, Xianjuan ZHANG, Fengjun LIU, Jun LI, Xiaoqiong ZHOU, Delei NIU, Yiquan LI, Wei WANG, Ning SHI, Ningyi JIN, Changzhan XIE, Xiaoni CUI, He ZHANG, Bin WANG, Huijun LU. Newcastle disease virus suppresses antigen presentation via inhibiting IL-12 expression in dendritic cells[J]. Journal of Zhejiang University Science B, 2024, 25(3): 254-270.

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author="Fulong NAN, Wenlong NAN, Xin YAN, Hui WANG, Shasha JIANG, Shuyun ZHANG, Zhongjie YU, Xianjuan ZHANG, Fengjun LIU, Jun LI, Xiaoqiong ZHOU, Delei NIU, Yiquan LI, Wei WANG, Ning SHI, Ningyi JIN, Changzhan XIE, Xiaoni CUI, He ZHANG, Bin WANG, Huijun LU",
journal="Journal of Zhejiang University Science B",
volume="25",
number="3",
pages="254-270",
year="2024",
publisher="Zhejiang University Press & Springer",
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%T Newcastle disease virus suppresses antigen presentation via inhibiting IL-12 expression in dendritic cells
%A Fulong NAN
%A Wenlong NAN
%A Xin YAN
%A Hui WANG
%A Shasha JIANG
%A Shuyun ZHANG
%A Zhongjie YU
%A Xianjuan ZHANG
%A Fengjun LIU
%A Jun LI
%A Xiaoqiong ZHOU
%A Delei NIU
%A Yiquan LI
%A Wei WANG
%A Ning SHI
%A Ningyi JIN
%A Changzhan XIE
%A Xiaoni CUI
%A He ZHANG
%A Bin WANG
%A Huijun LU
%J Journal of Zhejiang University SCIENCE B
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%@ 1673-1581
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%I Zhejiang University Press & Springer
%DOI 10.1631/jzus.B2300134

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T1 - Newcastle disease virus suppresses antigen presentation via inhibiting IL-12 expression in dendritic cells
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A1 - Zhongjie YU
A1 - Xianjuan ZHANG
A1 - Fengjun LIU
A1 - Jun LI
A1 - Xiaoqiong ZHOU
A1 - Delei NIU
A1 - Yiquan LI
A1 - Wei WANG
A1 - Ning SHI
A1 - Ningyi JIN
A1 - Changzhan XIE
A1 - Xiaoni CUI
A1 - He ZHANG
A1 - Bin WANG
A1 - Huijun LU
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VL - 25
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PB - Zhejiang University Press & Springer
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DOI - 10.1631/jzus.B2300134


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.

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1,南文龙2,焉鑫2,王惠1,江莎莎1,张树芸1,于忠杰7,张现娟1,刘俸君1,李俊1,周晓琼1,牛德磊1,李一权3,汪伟4,史宁5,金宁一6,解长占6,崔晓妮7,张赫6,王斌1,鲁会军6
1青岛大学基础医学院特种医学系,中国青岛市,266071
2中国动物卫生与流行病学中心,中国青岛市,266032
3长春中医药大学院士工作站,中国长春市,130117
4温州大学病毒学研究所,中国温州市,325035
5吉林大学动物医学学院,中国长春市,130012
6中国农业科学院长春兽医研究所,中国长春市,130122
7青岛华赛伯曼医学细胞生物有限公司,中国青岛市,266000
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。

关键词:新城疫病毒;树突状细胞;白介素12;T淋巴细胞;免疫抑制

Darkslateblue:Affiliate; Royal Blue:Author; Turquoise:Article

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