Dataset Information

Characterization of Influenza A Virus Infection in Mouse Pulmonary Stem/Progenitor Cells.

ABSTRACT: 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 in vitro cell model to characterize replication and pathogenic effects of influenza viruses in PSCs. First, mPSCs and its immortalized cell line mPSCsOct4+ 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)-? at 12 h and IFN-? 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.

SUBMITTER: Chao TL

PROVIDER: S-EPMC6985155 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Characterization of Influenza A Virus Infection in Mouse Pulmonary Stem/Progenitor Cells.

Chao Tai-Ling TL Gu Sing-Yi SY Lin Pi-Han PH Chou Yu-Tien YT Ling Thai-Yen TY Chang Sui-Yuan SY

Frontiers in microbiology 20200121

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 <i>in vitro</i> cell model to characterize replication and pathogenic effects of influenza viruses in PSCs. First, mPSCs and its immorta ...[more]

PMID: 32038512

Similar Datasets

Project description:Influenza Virus (IV) pneumonia is associated with severe damage of the lung epithelium and respiratory failure. Apart from efficient host defense, structural repair of the injured epithelium is crucial for survival of severe pneumonia. The molecular mechanisms underlying stem/progenitor cell mediated regenerative responses are not well characterized. In particular, the impact of IV infection on lung stem cells and their regenerative responses remains elusive. Our study demonstrates that a highly pathogenic IV infects various cell populations in the murine lung, but displays a strong tropism to an epithelial cell subset with high proliferative capacity, defined by the signature EpCamhighCD24lowintegrin(α6)high. This cell fraction expressed the stem cell antigen-1, highly enriched lung stem/progenitor cells previously characterized by the signature integrin(β4)+CD200+, and upregulated the p63/krt5 regeneration program after IV-induced injury. Using 3-dimensional organoid cultures derived from these epithelial stem/progenitor cells (EpiSPC), and in vivo infection models including transgenic mice, we reveal that their expansion, barrier renewal and outcome after IV-induced injury critically depended on Fgfr2b signaling. Importantly, IV infected EpiSPC exhibited severely impaired renewal capacity due to IV-induced blockade of β-catenin-dependent Fgfr2b signaling, evidenced by loss of alveolar tissue repair capacity after intrapulmonary EpiSPC transplantation in vivo. Intratracheal application of exogenous Fgf10, however, resulted in increased engagement of non-infected EpiSPC for tissue regeneration, demonstrated by improved proliferative potential, restoration of alveolar barrier function and increased survival following IV pneumonia. Together, these data suggest that tropism of IV to distal lung stem cell niches represents an important factor of pathogenicity and highlight impaired Fgfr2b signaling as underlying mechanism. Furthermore, increase of alveolar Fgf10 levels may represent a putative therapy to overcome regeneration failure after IV-induced lung injury.

Dataset Information

Characterization of Influenza A Virus Infection in Mouse Pulmonary Stem/Progenitor Cells.

Publications

Characterization of Influenza A Virus Infection in Mouse Pulmonary Stem/Progenitor Cells.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets