Novel prophylactic drugs and vaccination strategies for protection against influenza virus should induce specific effector T-cell immune responses in pulmonary airways and peripheral lymphoid organs. Designing approaches that promote T-cell-mediated responses and memory T-cell differentiation would strengthen host resistance to respiratory infectious diseases. The results of this study showed that pulmonary delivery of MENK via intranasal administration reduced viral titres, upregulated opioid receptor MOR and DOR, increased the proportions of T-cell subsets including CD8+ T cells, CD8+ TEM cells, NP/PA-effector CD8+ TEM cells in bronchoalveolar lavage fluid and lungs, and CD4+/CD8+ TCM cells in lymph nodes to protect mice against influenza viral challenge. Furthermore, we demonstrated that, on the 10th day of infection, the proportions of CD4+ TM and CD8+ TM cells were significantly increased, which meant that a stable TCM and TEM lineage was established in the early stage of influenza infection. Collectively, our data suggested that MENK administered intranasally, similar to the route of natural infection by influenza A virus, could exert antiviral activity through upregulating T-cell-mediated adaptive immune responses against influenza virus.

中文翻译：

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蛋氨酸脑啡肽 (MENK) 上调记忆 T 细胞抗流感反应

预防流感病毒的新型预防药物和疫苗接种策略应在肺气道和外周淋巴器官中诱导特异性效应 T 细胞免疫反应。设计促进 T 细胞介导的反应和记忆 T 细胞分化的方法将增强宿主对呼吸道传染病的抵抗力。本研究结果表明，通过鼻内给药向肺部输送MENK可降低病毒滴度，上调阿片受体MOR和DOR，增加T细胞亚群的比例，包括CD8+ T细胞、CD8+ TEM细胞、NP/PA效应CD8+ TEM细胞支气管肺泡灌洗液和肺部以及淋巴结中的 CD4+/CD8+ TCM 细胞可保护小鼠免受流感病毒的攻击。此外，我们还发现，在感染第10天，CD4+TM和CD8+TM细胞的比例显着增加，这意味着在流感感染的早期就建立了稳定的TCM和TEM谱系。总的来说，我们的数据表明，与甲型流感病毒自然感染途径类似，鼻内给药的 MENK 可以通过上调 T 细胞介导的针对流感病毒的适应性免疫反应来发挥抗病毒活性。