| First Author | Robinson KM | Year | 2013 |
| Journal | J Immunol | Volume | 191 |
| Issue | 10 | Pages | 5153-9 |
| PubMed ID | 24089191 | Mgi Jnum | J:206343 |
| Mgi Id | MGI:5550045 | Doi | 10.4049/jimmunol.1301237 |
| Citation | Robinson KM, et al. (2013) Influenza A exacerbates Staphylococcus aureus pneumonia by attenuating IL-1beta production in mice. J Immunol 191(10):5153-9 |
| abstractText | 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-1beta is known to regulate host defense, including playing a role in Th17 polarization. We examined whether IL-1beta signaling is required for S. aureus host defense and whether influenza infection impacted S. aureus-induced IL-1beta 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-1beta 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-kappaB activation, suggesting an inhibition of NF-kappaB-dependent transcription of pro-IL-1beta. Furthermore, overexpression of IL-1beta 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-1beta 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-1beta production, resulting in attenuation of Type 17 immunity and increased susceptibility to bacterial infection. |
