Influenza A exacerbates Staphylococcus aureus pneumonia by attenuating IL-1β production in mice.
نویسندگان
چکیده
Pneumonia is a leading cause of death worldwide. Staphylococcal aureus can be a cause of severe pneumonia alone or a common pathogen in secondary pneumonia following influenza. Recently, we reported that preceding influenza attenuated the Type 17 pathway, increasing the lung's susceptibility to secondary infection. IL-1β is known to regulate host defense, including playing a role in Th17 polarization. We examined whether IL-1β signaling is required for S. aureus host defense and whether influenza infection impacted S. aureus-induced IL-1β production and subsequent Type 17 pathway activation. Mice were challenged with S. aureus (USA 300), with or without preceding Influenza A/PR/8/34 H1N1 infection. IL-1R1(-/-) mice had significantly higher S. aureus burden, increased mortality, and decreased Type 17 pathway activation following S. aureus challenge. Coinfected mice had significantly decreased IL-1β production versus S. aureus infection alone at early time points following bacterial challenge. Preceding influenza did not attenuate S. aureus-induced inflammasome activation, but there was early suppression of NF-κB activation, suggesting an inhibition of NF-κB-dependent transcription of pro-IL-1β. Furthermore, overexpression of IL-1β in influenza and S. aureus-coinfected mice rescued the induction of IL-17 and IL-22 by S. aureus and improved bacterial clearance. Finally, exogenous IL-1β did not significantly rescue S. aureus host defense during coinfection in IL-17RA(-/-) mice or in mice in which IL-17 and IL-22 activity were blocked. These data reveal a novel mechanism by which Influenza A inhibits S. aureus-induced IL-1β production, resulting in attenuation of Type 17 immunity and increased susceptibility to bacterial infection.
منابع مشابه
Influenza A Exacerbates Staphylococcus aureus Pneumonia by Attenuating IL-1b Production in Mice
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عنوان ژورنال:
- Journal of immunology
دوره 191 10 شماره
صفحات -
تاریخ انتشار 2013