Abstract：
The vagus nerve circuit, operating through the alpha-7 nicotinic acetylcholine receptor (α7 nAChR), regulates the inflammatory response by influencing immune cells. However, the role of vagal-α7 nAChR signaling in influenza virus infection is unclear. In particular, does vagal-α7 nAChR signaling impact the infection of alveolar epithelial cells (AECs), the primary target cells of influenza virus? Here, we demonstrated a distinct role of α7 nAChR in type II AECs compared to its role in immune cells during influenza infection. We found that deletion of Chrna7 (encoding gene of α7 nAChR) in type II AECs or disruption of vagal circuits reduced lung influenza infection and protected mice from influenza-induced lung injury. We further unveiled that activation of α7 nAChR enhanced influenza infection through PTP1B-NEDD4L-ASK1-p38MAPK pathway. Mechanistically, activation of α7 nAChR signaling decreased p38MAPK phosphorylation during infection, facilitating the nuclear export of influenza viral ribonucleoproteins and thereby promoting infection. Taken together, our findings reveal a mechanism mediated by vagal-α7 nAChR signaling that promotes influenza viral infection and exacerbates disease severity. Targeting vagal-α7 nAChR signaling may offer novel strategies for combating influenza virus infections.
摘要：
迷走神经回路，通过α-7烟碱乙酰胆碱受体（α7nAChR）运作，通过影响免疫细胞调节炎症反应。然而,vagal-α7nAChR信号在流感病毒感染中的作用尚不清楚.特别是,迷走神经α7nAChR信号是否影响肺泡上皮细胞（AECs）的感染，流感病毒的主要靶细胞？这里，我们证明了α7nAChR在II型AECs中的独特作用与其在流感感染期间的免疫细胞中的作用相比.我们发现II型AECs中Chrna7（α7nAChR的编码基因）的缺失或迷走神经回路的破坏可减少肺部流感感染并保护小鼠免受流感引起的肺损伤。我们进一步揭示了α7nAChR的激活通过PTP1B-NEDD4L-ASK1-p38MAPK途径增强流感感染。机械上,α7nAChR信号的激活降低了感染期间p38MAPK的磷酸化，促进流感病毒核糖核蛋白的核出口，从而促进感染。一起来看,我们的研究结果揭示了由迷走神经α7nAChR信号介导的促进流感病毒感染和加重疾病严重程度的机制.靶向迷走神经-α7nAChR信号传导可能为对抗流感病毒感染提供新策略。
