Influenza A virus-mediated priming enhances cytokine secretion by human dendritic cells infected with Streptococcus
Thomas Kuri1, Anna Smed Sörensen, Saskia Thomas
1Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden.
Abstract:
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.
Insights
Influenza A virus primes immune cells, leading to increased IL-12p70 and IL-6 production upon secondary Streptococcus pneumoniae infection. Type I interferons are key drivers of this priming effect.
Area of Science:
- Immunology
- Virology
- Microbiology
Background:
- Secondary bacterial infections, particularly with Streptococcus pneumoniae (SP), following influenza A virus (IAV) infection pose significant global health challenges.
- The precise mechanisms underlying the exacerbated disease progression during these co-infections remain incompletely understood.
Purpose of the Study:
- To investigate the impact of IAV and SP co-infection on human monocyte-derived dendritic cells (MDDCs).
- To analyze the expression of key pro-inflammatory and immune-modulatory cytokines in response to these infections.
Main Methods:
- Analysis of cytokine expression (IL-12p70, IL-6) in MDDCs following IAV and/or SP infection.
- Investigation of factors influencing cytokine production, including time, dose, duration, pathogen viability, bacterial uptake, and endosome acidification.
- Assessment of the role of type I interferons in the observed immune response.
Main Results:
- IAV infection or exposure to IAV-infected cell supernatants primed MDDCs, enhancing IL-12p70 and IL-6 production upon subsequent SP infection.
- This priming effect was independent of simultaneous co-infection but dependent on infection parameters and bacterial factors.
- Bacterially infected cells were identified as the primary producers of IL-12p70.
- Type I interferons were identified as the main mediators responsible for IAV-induced priming of IL-12p70.
Conclusions:
- IAV infection primes dendritic cells, altering their cytokine response to subsequent SP infection, which may explain elevated cytokine levels in co-infected patients.
- Type I interferons play a crucial role in mediating this priming effect.
- These findings offer insights into the pathogenesis of IAV-SP co-infections and their clinical implications.
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