Chen Bei, Chen Chunjing, Lu Fangguo, Wang Xiaoqi, Zhang Xianggang, Wang Zhibin, Liu Huihui
Medical School, Hunan University of Chinese Medicine, Changsha 410208, China.
School of Integrated Chinese and Western Medicine, Hunan University of Chinese Medicine, Changsha 410208, China.
Microorganisms. 2025 May 24;13(6):1201. doi: 10.3390/microorganisms13061201.
Influenza A virus (IAV) is a major cause of respiratory illness in humans and animals. Secondary bacterial infections, especially those caused by (SA), significantly increase influenza-related morbidity and mortality. However, the mechanisms underlying these co-infections remain unclear. In this study, we examined how IAV infection influences SA-induced inflammation in lung epithelial cells. Our study was conducted based on in vitro experiments. First, we infected MLE-12 cells with IAV, confirming viral replication and the resulting cell damage. SA was then introduced 24 h or 36 h post-infection, and the cellular responses were measured. We assessed cell viability, cell-free DNA, Citrullinated histone H3, and the mRNA expression of TLR4 and proinflammatory cytokines. Our results showed that IAV+SA stimulation significantly increased upregulated TLR4 expression and inflammatory damage. To further explore TLR4's role, we used the inhibitor TAK-242 and a TLR4 siRNA knockdown. Both approaches reduced the inflammatory response triggered by IAV and SA stimulation. These findings suggest that TLR4 is a key mediator in the enhanced inflammation observed during IAV and SA co-infection, offering a potential target for therapeutic intervention.
甲型流感病毒（IAV）是人类和动物呼吸道疾病的主要病因。继发性细菌感染，尤其是由金黄色葡萄球菌（SA）引起的感染，会显著增加流感相关的发病率和死亡率。然而，这些合并感染背后的机制仍不清楚。在本研究中，我们研究了IAV感染如何影响SA诱导的肺上皮细胞炎症。我们的研究基于体外实验进行。首先，我们用IAV感染MLE-12细胞，确认病毒复制及由此导致的细胞损伤。然后在感染后24小时或36小时引入SA，并测量细胞反应。我们评估了细胞活力、游离DNA、瓜氨酸化组蛋白H3以及TLR4和促炎细胞因子的mRNA表达。我们的结果表明，IAV+SA刺激显著增加了TLR4表达上调和炎症损伤。为了进一步探索TLR4的作用，我们使用了抑制剂TAK-242和TLR4 siRNA敲低。这两种方法都降低了IAV和SA刺激引发的炎症反应。这些发现表明，TLR4是IAV和SA合并感染期间观察到的炎症增强的关键介质，为治疗干预提供了一个潜在靶点。
