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NDV entry into dendritic cells through macropinocytosis and suppression of T lymphocyte proliferation
Virology ( IF 2.8 ) Pub Date : 2018-03-15 , DOI: 10.1016/j.virol.2018.02.011
Lei Tan , Yuqiang Zhang , Changtao Qiao , Yanmei Yuan , Yingjie Sun , Xusheng Qiu , Chunchun Meng , Cuiping Song , Ying Liao , Muhammad Munir , Venugopal Nair , Zhuang Ding , Xiufan Liu , Chan Ding

Newcastle disease virus (NDV) causes major economic losses in the poultry industry. Previous studies have shown that NDV utilizes different pathways to infect various cells, including dendritic cells (DCs). Here, we demonstrate that NDV gains entry into DCs mainly via macropinocytosis and clathrin-mediated endocytosis. The detection of cytokines interferon-γ (IFN-γ), tumor necrosis factor-α (TNF-α), interleukin-12 (IL-12), interleukin-4 (IL-4) and interleukin-10 (IL-10) indicates that NDV significantly induces Th1 responses and lowers Th2 responses. Furthermore, NDV entry into DCs resulted in the upregulation of TNF-related apoptosis-inducing ligand (TRAIL) and cleaved caspase-3 proteins, which in turn activated the extrinsic apoptosis pathway and induced DCs apoptosis. Transwell® co-culture demonstrated that direct contact between live NDV-stimulated DCs and T cells, rather than heated-inactivated NDV, inhibited CD4+ T cell proliferation. Taken together, these findings provide new insights into the mechanism underlying NDV infections, particularly in relation to antigen presentation cells and suppression of T cell proliferation.



中文翻译:

NDV通过巨胞饮作用和抑制T淋巴细胞增殖进入树突状细胞

新城疫病毒(NDV)在家禽业中造成重大经济损失。先前的研究表明,NDV利用不同的途径感染包括树突状细胞(DC)在内的各种细胞。在这里,我们证明NDV主要通过巨胞饮和网格蛋白介导的内吞作用进入DC。检测细胞因子干扰素-γ(IFN-γ),肿瘤坏死因子-α(TNF-α),白介素12(IL-12),白介素4(IL-4)和白介素10(IL-10)表明NDV显着诱导Th1反应,降低Th2反应。此外,NDV进入DC导致TNF相关凋亡诱导配体(TRAIL)和裂解的caspase-3蛋白上调,从而激活外在凋亡途径并诱导DCs凋亡。+ T细胞增殖。综上所述,这些发现为NDV感染的潜在机制提供了新的见解,特别是与抗原呈递细胞和T细胞增殖的抑制有关。

更新日期:2018-03-15
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