The Role of TLR4 in Lung Epithelial Cell Injury Caused by Influenza Virus Combined with Staphylococcus aureus

作者：Bei Chen, Chunjing Chen, Lu Fangguo, Xiaoqi Wang, Xianggang Zhang, Zhibin Wang, Huihui Liu · 发表于：Microorganisms · 年份：2025 · DOI：10.3390/microorganisms13061201 · 被引用次数：4 · 研究领域：Respiratory viral infections research、Immune Response and Inflammation、Pediatric health and respiratory diseases

(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.