• Open Access

Influenza A virus-mediated priming enhances cytokine secretion by human dendritic cells infected with Streptococcus pneumoniae

Authors

  • Thomas Kuri,

    1. Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden
    2. Department of Laboratory Medicine, Division of Clinical Microbiology, Karolinska University Hospital, Stockholm, Sweden
    Search for more papers by this author
  • Anna Smed Sörensen,

    1. Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden
    Search for more papers by this author
  • Saskia Thomas,

    1. Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden
    Search for more papers by this author
  • Gunilla B. Karlsson Hedestam,

    1. Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden
    Search for more papers by this author
  • Staffan Normark,

    1. Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden
    2. Department of Laboratory Medicine, Division of Clinical Microbiology, Karolinska University Hospital, Stockholm, Sweden
    Search for more papers by this author
  • Birgitta Henriques-Normark,

    1. Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden
    2. Department of Laboratory Medicine, Division of Clinical Microbiology, Karolinska University Hospital, Stockholm, Sweden
    Search for more papers by this author
  • Gerald M. McInerney,

    1. Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden
    Search for more papers by this author
  • Laura Plant

    Corresponding author
    1. Department of Laboratory Medicine, Division of Clinical Microbiology, Karolinska University Hospital, Stockholm, Sweden
    • Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden
    Search for more papers by this author

For correspondence. E-mail laura.plant@ki.se; Tel. (+46) 8 51771208; Fax (+46) 8 304 276.

Summary

Secondary infections with Streptococcus pneumoniae (SP) are frequently observed following influenza A virus (IAV) infection and have a substantial impact on global health. Despite this, the basis for the disease progression is incompletely understood. To investigate the effect of co-infection on human monocyte-derived dendritic cells (MDDCs) we analysed the expression of clinically important pro-inflammatory and immune-modulatory cytokines. IAV infection or treatment with supernatants from IAV-infected cell cultures resulted in priming of the DCs which subsequently influenced the production of IL-12p70, as well as IL-6, following SP infection. Co-infection of the same cell was not required but this effect was dependent on the time, dose and duration of the infections, as well as pathogen viability, bacterial uptake and endosome acidification. Bacterially infected cells were characterized as the main producers of IL-12p70. Finally, we showed that type I interferons were primarily responsible for the priming of IL-12p70 that was observed by infection with IAV. These results provide a probable mechanism for the elevated levels of particular cytokines observed in IAV and SP co-infected cell cultures with implications for the pathogenic outcome observed during in vivo infection.

Ancillary