title: The role of IL-27 in susceptibility to post-influenza Staphylococcus aureus pneumonia.
abstract: BACKGROUND
  Influenza is a common respiratory virus and Staphylococcus aureus frequently causes secondary pneumonia during influenza infection, leading to increased morbidity and mortality. Influenza has been found to attenuate subsequent Type 17 immunity, enhancing susceptibility to secondary bacterial infections. IL-27 is known to inhibit Type 17 immunity, suggesting a potential critical role for IL-27 in viral and bacterial co-infection.
  
  
  METHODS
  A murine model of influenza and Staphylococcus aureus infection was used to mimic human viral, bacterial co-infection. C57BL/6 wild-type, IL-27 receptor α knock-out, and IL-10 knock-out mice were infected with Influenza H1N1 (A/PR/8/34) or vehicle for 6 days followed by challenge with Staphylococcus aureus or vehicle for 24 hours. Lung inflammation, bacterial burden, gene expression, and cytokine production were determined.
  
  
  RESULTS
  IL-27 receptor α knock-out mice challenged with influenza A had increased morbidity compared to controls, but no change in viral burden. IL-27 receptor α knock-out mice infected with influenza displayed significantly decreased IL-10 production compared to wild-type. IL-27 receptor α knock-out mice co-infected with influenza and S. aureus had improved bacterial clearance compared to wild-type controls. Importantly, there were significantly increased Type 17 responses and decreased IL-10 production in IL-27 receptor α knock-out mice. Dual infected IL-10-/- mice had significantly less bacterial burden compared to dual infected WT mice.
  
  
  CONCLUSIONS
  These data reveal that IL-27 regulates enhanced susceptibility to S. aureus pneumonia following influenza infection, potentially through the induction of IL-10 and suppression of IL-17.
authors: Department of Pediatrics, Children's Hospital of Pittsburgh of UPMC, Pittsburgh, PA, USA. robinsonkm@upmc.edu.|Department of Medicine, University of Pittsburgh Medical Center, Pittsburgh, PA, USA. robinsonkm@upmc.edu.
authors: Keven M
authors: KM
authors: Robinson
authors: Department of Pediatrics, Children's Hospital of Pittsburgh of UPMC, Pittsburgh, PA, USA. benjamin.lee3@chp.edu.
authors: Benjamin
authors: B
authors: Lee
authors: Department of Pediatrics, Children's Hospital of Pittsburgh of UPMC, Pittsburgh, PA, USA. erich.scheller@gmail.com.
authors: Erich V
authors: EV
authors: Scheller
authors: Department of Pediatrics, Children's Hospital of Pittsburgh of UPMC, Pittsburgh, PA, USA. sivanarayana.mandalapu@chp.edu.
authors: Sivanarayana
authors: S
authors: Mandalapu
authors: Department of Medicine, Dartmouth Medical School, Lebanon, NH, USA. richard.i.enelow@dartmouth.edu.
authors: Richard I
authors: RI
authors: Enelow
authors: Richard K. Mellon Foundation Institute, Children's Hospital of Pittsburgh of UPMC, Pittsburgh, PA, USA. jay.kolls@chp.edu.
authors: Jay K
authors: JK
authors: Kolls
authors: Department of Pediatrics, Children's Hospital of Pittsburgh of UPMC, Pittsburgh, PA, USA. john.alcorn@chp.edu.
authors: John F
authors: JF
authors: Alcorn
mesh_terms: D000818:Animals; D058491:Bacterial Load; D060085:Coinfection; D004195:Disease Models, Animal; D054884:Host-Pathogen Interactions; D007111:Immunity, Cellular; D053118:Influenza A Virus, H1N1 Subtype / Q000276:immunology* / Q000472:pathogenicity; D016753:Interleukin-10 / Q000172:deficiency / Q000235:genetics; D020381:Interleukin-17 / Q000276:immunology; D007378:Interleukins / Q000276:immunology*; D008168:Lung / Q000276:immunology* / Q000382:microbiology / Q000821:virology; D008297:Male; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009976:Orthomyxoviridae Infections / Q000276:immunology* / Q000821:virology; D011023:Pneumonia, Staphylococcal / Q000235:genetics / Q000276:immunology* / Q000382:microbiology; D018121:Receptors, Cytokine / Q000172:deficiency / Q000235:genetics; D018123:Receptors, Interleukin; D013211:Staphylococcus aureus / Q000276:immunology* / Q000472:pathogenicity; D058504:Th17 Cells / Q000276:immunology / Q000382:microbiology / Q000821:virology; D013997:Time Factors; D019562:Viral Load
chemical_list: C556062:IL10 protein, mouse; C486767:Il27 protein, mouse; C484747:Il27ra protein, mouse; D020381:Interleukin-17; D007378:Interleukins; D018121:Receptors, Cytokine; D018123:Receptors, Interleukin; D016753:Interleukin-10
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