The Role of TLR4 in Lung Epithelial Cell Injury Caused by Influenza Virus Combined with <i>Staphylococcus aureus</i>
Influenza A virus (IAV) is a major cause of respiratory illness in humans and animals. Secondary bacterial infections, especially those caused by <i>Staphylococcus aureus</i> (SA), significantly increase influenza-related morbidity and mortality. However, the mechanisms underlying these...
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| Language: | English |
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MDPI AG
2025-05-01
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| Series: | Microorganisms |
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| Online Access: | https://www.mdpi.com/2076-2607/13/6/1201 |
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| author | Bei Chen Chunjing Chen Fangguo Lu Xiaoqi Wang Xianggang Zhang Zhibin Wang Huihui Liu |
| author_facet | Bei Chen Chunjing Chen Fangguo Lu Xiaoqi Wang Xianggang Zhang Zhibin Wang Huihui Liu |
| author_sort | Bei Chen |
| collection | DOAJ |
| description | Influenza A virus (IAV) is a major cause of respiratory illness in humans and animals. Secondary bacterial infections, especially those caused by <i>Staphylococcus aureus</i> (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. |
| format | Article |
| id | doaj-art-ac7fa9fe403447ebaf830b533e27e468 |
| institution | Kabale University |
| issn | 2076-2607 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Microorganisms |
| spelling | doaj-art-ac7fa9fe403447ebaf830b533e27e4682025-08-20T03:27:32ZengMDPI AGMicroorganisms2076-26072025-05-01136120110.3390/microorganisms13061201The Role of TLR4 in Lung Epithelial Cell Injury Caused by Influenza Virus Combined with <i>Staphylococcus aureus</i>Bei Chen0Chunjing Chen1Fangguo Lu2Xiaoqi Wang3Xianggang Zhang4Zhibin Wang5Huihui Liu6Medical School, Hunan University of Chinese Medicine, Changsha 410208, ChinaMedical School, Hunan University of Chinese Medicine, Changsha 410208, ChinaMedical School, Hunan University of Chinese Medicine, Changsha 410208, ChinaSchool of Integrated Chinese and Western Medicine, Hunan University of Chinese Medicine, Changsha 410208, ChinaSchool of Integrated Chinese and Western Medicine, Hunan University of Chinese Medicine, Changsha 410208, ChinaSchool of Integrated Chinese and Western Medicine, Hunan University of Chinese Medicine, Changsha 410208, ChinaMedical School, Hunan University of Chinese Medicine, Changsha 410208, ChinaInfluenza A virus (IAV) is a major cause of respiratory illness in humans and animals. Secondary bacterial infections, especially those caused by <i>Staphylococcus aureus</i> (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.https://www.mdpi.com/2076-2607/13/6/1201influenza A virus<i>Staphylococcus aureus</i>secondary infectioninflammatory factorcell trauma |
| spellingShingle | Bei Chen Chunjing Chen Fangguo Lu Xiaoqi Wang Xianggang Zhang Zhibin Wang Huihui Liu The Role of TLR4 in Lung Epithelial Cell Injury Caused by Influenza Virus Combined with <i>Staphylococcus aureus</i> Microorganisms influenza A virus <i>Staphylococcus aureus</i> secondary infection inflammatory factor cell trauma |
| title | The Role of TLR4 in Lung Epithelial Cell Injury Caused by Influenza Virus Combined with <i>Staphylococcus aureus</i> |
| title_full | The Role of TLR4 in Lung Epithelial Cell Injury Caused by Influenza Virus Combined with <i>Staphylococcus aureus</i> |
| title_fullStr | The Role of TLR4 in Lung Epithelial Cell Injury Caused by Influenza Virus Combined with <i>Staphylococcus aureus</i> |
| title_full_unstemmed | The Role of TLR4 in Lung Epithelial Cell Injury Caused by Influenza Virus Combined with <i>Staphylococcus aureus</i> |
| title_short | The Role of TLR4 in Lung Epithelial Cell Injury Caused by Influenza Virus Combined with <i>Staphylococcus aureus</i> |
| title_sort | role of tlr4 in lung epithelial cell injury caused by influenza virus combined with i staphylococcus aureus i |
| topic | influenza A virus <i>Staphylococcus aureus</i> secondary infection inflammatory factor cell trauma |
| url | https://www.mdpi.com/2076-2607/13/6/1201 |
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