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The role of IL-27 in susceptibility to post-influenza Staphylococcus aureus pneumonia

Robinson, KM and Lee, B and Scheller, EV and Mandalapu, S and Enelow, RI and Kolls, JK and Alcorn, JF (2015) The role of IL-27 in susceptibility to post-influenza Staphylococcus aureus pneumonia. Respiratory Research, 16 (1). ISSN 1465-9921

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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.


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Details

Item Type: Article
Status: Published
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Robinson, KMkmr82@pitt.eduKMR82
Lee, B
Scheller, EV
Mandalapu, S
Enelow, RI
Kolls, JKjkk23@pitt.eduJKK23
Alcorn, JFjfa9@pitt.eduJFA9
Date: 5 February 2015
Date Type: Publication
Journal or Publication Title: Respiratory Research
Volume: 16
Number: 1
DOI or Unique Handle: 10.1186/s12931-015-0168-8
Schools and Programs: School of Medicine > Medicine
School of Medicine > Pediatrics
Refereed: Yes
ISSN: 1465-9921
Date Deposited: 22 Dec 2016 15:35
Last Modified: 30 Mar 2021 14:55
URI: http://d-scholarship.pitt.edu/id/eprint/29412

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