| Popis: |
Influenza is an annual, global healthcare concern. Secondary bacterial pneumonia is a severe complication associated with primary influenza virus infection that often results in critical morbidity and mortality. We have identified influenza-induced suppression of antibacterial type 17 immunity as a mechanism for enhanced susceptibility to bacterial superinfection. We have shown that influenza-induced type I IFN impairs type 17 activation. STAT1 is a transcription factor involved in IFN signaling that is shared by types I, II, and III IFN. In this study, we investigated the role of STAT1 signaling during influenza and methicillin-resistant Staphylococcus aureus superinfection. STAT1−/− mice had increased morbidity and airway inflammation compared with control mice during influenza monoinfection. Despite this worsened antiviral response, STAT1−/− mice were protected from superinfection bacterial burden and mortality compared with controls. Type 17 immune activation was increased in lymphocytes in STAT1−/− mice during superinfection. The elevation in type 17 immunity was not related to increased IL-23 production, because type I IFN could inhibit IL-23 expression in a STAT1-independent manner. STAT1−/− APCs were inherently biased toward type 17 polarization compared with control cells. Further, STAT1−/− dendritic cells produced attenuated IL-6 and TNF-α upon heat-killed S. aureus stimulation compared with control. Overall, these data indicate that STAT1 signaling plays a detrimental role in influenza and methicillin-resistant Staphylococcus aureus superinfection by controlling the magnitude of type 17 immune activation. |
