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Human Blood and Tonsil Plasmacytoid Dendritic Cells Display Similar Gene Expression Profiles but Exhibit Differential Type I IFN Responses to Influenza A Virus Infection

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  • Human Blood and Tonsil Plasmacytoid Dendritic Cells Display Similar Gene Expression Profiles but Exhibit Differential Type I IFN Responses to Influenza A Virus Infection

    J Immunol. 2019 Feb 13. pii: ji1801191. doi: 10.4049/jimmunol.1801191. [Epub ahead of print]
    Human Blood and Tonsil Plasmacytoid Dendritic Cells Display Similar Gene Expression Profiles but Exhibit Differential Type I IFN Responses to Influenza A Virus Infection.

    Vangeti S1, Gertow J1, Yu M1, Liu S1, Baharom F1, Scholz S1, Friberg D2, Starkhammar M3, Ahlberg A4, Smed-S?rensen A5.
    Author information

    Abstract

    Influenza A virus (IAV) infection constitutes an annual health burden across the globe. Plasmacytoid dendritic cells (PDCs) are central in antiviral defense because of their superior capacity to produce type I IFNs in response to viruses. Dendritic cells (DCs) differ depending on their anatomical location. However, only limited host-pathogen data are available from the initial site of infection in humans. In this study, we investigated how human tonsil PDCs, likely exposed to virus because of their location, responded to IAV infection compared with peripheral blood PDCs. In tonsils, unlike in blood, PDCs are the most frequent DC subset. Both tonsil and blood PDCs expressed several genes necessary for pathogen recognition and immune response, generally in a similar pattern. MxA, a protein that renders cells resistant to IAV infection, was detected in both tonsil and blood PDCs. However, despite steady-state MxA expression and contrary to previous reports, at high IAV concentrations (typically cytopathic to other immune cells), both tonsil and blood PDCs supported IAV infection. IAV exposure resulted in PDC maturation by upregulation of CD86 expression and IFN-α secretion. Interestingly, blood PDCs secreted 10-fold more IFN-α in response to IAV compared with tonsil PDCs. Tonsil PDCs also had a dampened cytokine response to purified TLR ligands compared with blood PDCs. Our findings suggest that tonsil PDCs may be less responsive to IAV than blood PDCs, highlighting the importance of studying immune cells at their proposed site of function.
    Copyright ? 2019 by The American Association of Immunologists, Inc.


    PMID: 30760619 DOI: 10.4049/jimmunol.1801191
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