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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
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.
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。
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.
新城疫病毒树突状细胞白介素12T淋巴细胞免疫抑制
Newcastle disease virusDendritic cellsInterleukin-12 (IL-12)T cellsImmunosuppression
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