tetano
Editor, Senior Moderator
J Immunol. 2013 Oct 2. [Epub ahead of print]
Influenza A Exacerbates Staphylococcus aureus Pneumonia by Attenuating IL-1β Production in Mice.
Robinson KM, Choi SM, McHugh KJ, Mandalapu S, Enelow RI, Kolls JK, Alcorn JF.
Source
Department of Pediatrics, Children's Hospital of Pittsburgh of University of Pittsburgh Medical Center, Pittsburgh, PA 15224;
Abstract
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.
PMID:
24089191
[PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/24089191
Influenza A Exacerbates Staphylococcus aureus Pneumonia by Attenuating IL-1β Production in Mice.
Robinson KM, Choi SM, McHugh KJ, Mandalapu S, Enelow RI, Kolls JK, Alcorn JF.
Source
Department of Pediatrics, Children's Hospital of Pittsburgh of University of Pittsburgh Medical Center, Pittsburgh, PA 15224;
Abstract
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.
PMID:
24089191
[PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/24089191