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Unique transcriptional architecture in airway epithelial cells and macrophages shapes distinct responses following influenza virus infection ex vivo

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  • Unique transcriptional architecture in airway epithelial cells and macrophages shapes distinct responses following influenza virus infection ex vivo

    J Virol. 2019 Jan 9. pii: JVI.01986-18. doi: 10.1128/JVI.01986-18. [Epub ahead of print]
    Unique transcriptional architecture in airway epithelial cells and macrophages shapes distinct responses following influenza virus infection ex vivo.

    Ma JZ1, Ng WC2, Zappia L3, Gearing LJ4, Olshansky M5, Pham K4, Cheong K4, Hsu A4, Turner SJ5, Wijburg O2, Londrigan SL2, Brooks AG2, Reading PC1,6.
    Author information

    Abstract

    Airway epithelial cells and macrophages differ markedly in their responses to influenza A virus (IAV) infection. To investigate transcriptional responses underlying these differences, purified subsets of type II airway epithelial cells (ATII) and alveolar macrophages (AM) recovered from the lungs of mock- or IAV-infected mice at 9 hours post-infection were subjected to RNA sequencing. This time point was chosen to allow for characterization of cell types first infected with virus inoculum, prior to multicycle virus replication and the infiltration of inflammatory cells into the airways. In the absence of infection, AM predominantly expressed genes related to immunity whereas ATII expressed genes consistent with their physiological roles in the lung. Following IAV infection, AM almost exclusively activated cell-intrinsic antiviral pathways that were dependent on interferon regulatory factor (IRF)3/7 and/or type I interferon (IFN) signaling. In contrast, IAV-infected ATII activated a broader range of physiological responses, including cell-intrinsic antiviral pathways, which were both independent and dependent on IRF3/7 and/or type I IFN. These data suggest that transcriptional profiles hardwired during development are a major determinant underlying the different responses of ATII and AM to IAV infection.IMPORTANCE Airway epithelial cells (AEC) and airway macrophages (AM) represent major targets of influenza A virus (IAV) infection in the lung, yet the two cell types respond very differently to IAV infection. We have used RNA sequencing to define the host transcriptional responses in each cell type under steady-state conditions, as well as following IAV infection. To do this, different cell subsets isolated from the lungs of mock- and IAV-infected mice were subjected to RNA sequencing. Under steady-state conditions, AM and AEC express distinct transcriptional activity, consistent with distinct physiological roles in the airways. Not surprisingly, these also exhibited major differences in transcriptional responses following IAV infection. These studies shed light on how the different transcriptional architecture of airway cells from two different lineages drive transcriptional responses to IAV infection.
    Copyright 2019 American Society for Microbiology.


    PMID: 30626665 DOI: 10.1128/JVI.01986-18
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