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

• Published in: Journal of Zhejiang University. B. Science Vol. 25; no. 3; pp. 254 - 270
• Main Authors: Nan, Fulong, Nan, Wenlong, Yan, Xin, Wang, Hui, Jiang, Shasha, Zhang, Shuyun, Yu, Zhongjie, Zhang, Xianjuan, Liu, Fengjun, Li, Jun, Zhou, Xiaoqiong, Niu, Delei, Li, Yiquan, Wang, Wei, Shi, Ning, Jin, Ningyi, Xie, Changzhan, Cui, Xiaoni, Zhang, He, Wang, Bin, Lu, Huijun
• Format: Journal Article
• Language: English
• Published: Hangzhou Zhejiang University Press 01.03.2024; Springer Nature B.V; Department of Special Medicine,Department of Pathogenic Biology,School of Basic Medicine,Qingdao University,Qingdao 266071,China%China Animal Health and Epidemiology Center,Qingdao 266032,China%Sino-Cell Biomed Co.,Ltd.,Qingdao 266000,China%Academician Workstation of Jilin Province,Changchun University of Chinese Medicine,Changchun 130117,China%Institute of Virology,Wenzhou University,Wenzhou 325035,China%College of Veterinary Medicine,Jilin University,Changchun 130012,China%Changchun Veterinary Research Institute,Chinese Academy of Agricultural Sciences,Changchun 130122,China
• Subjects: Animals; Antigen Presentation; Antigens; Biomedical and Life Sciences; Biomedicine; Cell proliferation; Dendritic Cells; Enzyme-linked immunosorbent assay; Flow cytometry; Immune system; Immunoblotting; Immunomodulation; Immunosuppression; Interleukin-12 - pharmacology; Interleukins; Kinases; Lipopolysaccharides; Lymphocytes; Lymphocytes T; MAP kinase; Newcastle disease; Newcastle disease virus - physiology; Polymerase chain reaction; Research Article; Tumor necrosis factor-TNF; Tumor necrosis factor-α; Vaccine development; Vaccines; Vaccines - pharmacology; Viruses; γ-Interferon; Immunosuppression; 新城疫病毒; Dendritic cells; 树突状细胞; 免疫抑制; Newcastle disease virus; Interleukin-12 (IL-12); T cells; T淋巴细胞; 白介素12; Interleukin-12(IL-12)
• DOI: 10.1631/jzus.B2300134
• ISSN: 1673-1581; 1862-1783

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.