Chao Tai-Ling, Gu Sing-Yi, Lin Pi-Han, Chou Yu-Tien, Ling Thai-Yen, Chang Sui-Yuan
Department of Clinical Laboratory Sciences and Medical Biotechnology, National Taiwan University College of Medicine, Taipei, Taiwan.
Department of Pharmacology, National Taiwan University College of Medicine, Taipei, Taiwan.
Front Microbiol. 2020 Jan 21;10:2942. doi: 10.3389/fmicb.2019.02942. eCollection 2019.
The pulmonary stem/progenitor cells, which could be differentiated into downstream cells to repair tissue damage caused by influenza A virus, have also been shown to be the target cells of influenza virus infection. In this study, mouse pulmonary stem/progenitor cells (mPSCs) with capability to differentiate into type I or type II alveolar cells were used as an cell model to characterize replication and pathogenic effects of influenza viruses in PSCs. First, mPSCs and its immortalized cell line mPSCs were shown to be susceptible to PR8, seasonal H1N1, 2009 pandemic H1N1, and H7N9 influenza viruses and can generate infectious virus particles, although with a lower virus titer, which could be attributed by the reduced vRNA replication and nucleoprotein (NP) aggregation in the cytoplasm. Nevertheless, a significant increase of interleukin (IL)-6 and interferon (IFN)-γ at 12 h and IFN-β at 24 h post infection in mPSCs implicates that mPSCs might function as a sensor to modulate immune responses to influenza virus infection. In summary, our results demonstrated mPSCs, as one of the target cells for influenza A viruses, could modulate early proinflammatory responses to influenza virus infection.
肺干/祖细胞能够分化为下游细胞以修复甲型流感病毒引起的组织损伤,同时也被证明是流感病毒感染的靶细胞。在本研究中,具有分化为I型或II型肺泡细胞能力的小鼠肺干/祖细胞(mPSCs)被用作细胞模型,以表征流感病毒在肺干/祖细胞中的复制和致病作用。首先,mPSCs及其永生化细胞系mPSCs被证明对PR8、季节性H1N1、2009年大流行H1N1和H7N9流感病毒敏感,并且能够产生传染性病毒颗粒,尽管病毒滴度较低,这可能归因于细胞质中vRNA复制和核蛋白(NP)聚集的减少。然而,感染后12小时mPSCs中白细胞介素(IL)-6和干扰素(IFN)-γ显著增加,24小时IFN-β显著增加,这表明mPSCs可能作为一种传感器来调节对流感病毒感染的免疫反应。总之,我们的结果表明,mPSCs作为甲型流感病毒的靶细胞之一,可以调节对流感病毒感染的早期促炎反应。