tetano
Editor, Senior Moderator
Mucosal Immunol. 2019 Jul 11. doi: 10.1038/s41385-019-0188-7. [Epub ahead of print]
[h=1]IL-22-binding protein exacerbates influenza, bacterial super-infection.[/h] Abood RN[SUP]1[/SUP], McHugh KJ[SUP]1[/SUP], Rich HE[SUP]1[/SUP], Ortiz MA[SUP]1[/SUP], Tobin JM[SUP]1[/SUP], Ramanan K[SUP]1[/SUP], Robinson KM[SUP]2[/SUP], Bomberger JM[SUP]3[/SUP], Kolls JK[SUP]4[/SUP], Manni ML[SUP]1[/SUP], Pociask DA[SUP]5[/SUP], Alcorn JF[SUP]6[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] Secondary bacterial pneumonia is a significant complication of severe influenza infection and Staphylococcus aureus and Streptococcus pneumoniae are the primary pathogens of interest. IL-22 promotes S. aureus and S. pneumoniae host defense in the lung through epithelial integrity and induction of antimicrobial peptides and is inhibited by the soluble decoy receptor IL-22-binding protein (IL-22BP). Little is known about the effect of the IL-22/IL-22BP regulatory pathway on lung infection, and it has not been studied in the setting of super-infection. We exposed wild-type and IL-22BP[SUP]-/-[/SUP] mice to influenza A/PR/8/34 for 6 days prior to infection with S. aureus (USA300) S. pneumoniae. Super-infected IL-22BP[SUP]-/-[/SUP] mice had decreased bacterial burden and improved survival compared to controls. IL-22BP[SUP]-/-[/SUP] mice exhibited decreased inflammation, increased lipocalin 2 expression, and deletion of IL-22BP was associated with preserved epithelial barrier function with evidence of improved tight junction stability. Human bronchial epithelial cells treated with IL-22Fc showed evidence of improved tight junctions compared to untreated cells. This study revealed that IL-22BP[SUP]-/-[/SUP] mice are protected during influenza, bacterial super-infection, suggesting that IL-22BP has a pro-inflammatory role and impairs epithelial barrier function likely through interaction with IL-22.
PMID: 31296910 DOI: 10.1038/s41385-019-0188-7
[h=1]IL-22-binding protein exacerbates influenza, bacterial super-infection.[/h] Abood RN[SUP]1[/SUP], McHugh KJ[SUP]1[/SUP], Rich HE[SUP]1[/SUP], Ortiz MA[SUP]1[/SUP], Tobin JM[SUP]1[/SUP], Ramanan K[SUP]1[/SUP], Robinson KM[SUP]2[/SUP], Bomberger JM[SUP]3[/SUP], Kolls JK[SUP]4[/SUP], Manni ML[SUP]1[/SUP], Pociask DA[SUP]5[/SUP], Alcorn JF[SUP]6[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] Secondary bacterial pneumonia is a significant complication of severe influenza infection and Staphylococcus aureus and Streptococcus pneumoniae are the primary pathogens of interest. IL-22 promotes S. aureus and S. pneumoniae host defense in the lung through epithelial integrity and induction of antimicrobial peptides and is inhibited by the soluble decoy receptor IL-22-binding protein (IL-22BP). Little is known about the effect of the IL-22/IL-22BP regulatory pathway on lung infection, and it has not been studied in the setting of super-infection. We exposed wild-type and IL-22BP[SUP]-/-[/SUP] mice to influenza A/PR/8/34 for 6 days prior to infection with S. aureus (USA300) S. pneumoniae. Super-infected IL-22BP[SUP]-/-[/SUP] mice had decreased bacterial burden and improved survival compared to controls. IL-22BP[SUP]-/-[/SUP] mice exhibited decreased inflammation, increased lipocalin 2 expression, and deletion of IL-22BP was associated with preserved epithelial barrier function with evidence of improved tight junction stability. Human bronchial epithelial cells treated with IL-22Fc showed evidence of improved tight junctions compared to untreated cells. This study revealed that IL-22BP[SUP]-/-[/SUP] mice are protected during influenza, bacterial super-infection, suggesting that IL-22BP has a pro-inflammatory role and impairs epithelial barrier function likely through interaction with IL-22.
PMID: 31296910 DOI: 10.1038/s41385-019-0188-7