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IL-22-binding protein exacerbates influenza, bacterial super-infection

Robert N Abood1, Kevin J McHugh1, Helen E Rich1

  • 1Department of Pediatrics, UPMC Children's Hospital of Pittsburgh, Pittsburgh, PA, USA.

Mucosal Immunology
|July 13, 2019
PubMed

Insights

Removing IL-22-binding protein (IL-22BP) protected mice against influenza and secondary bacterial super-infections by improving lung epithelial barrier function and reducing inflammation.

Area of Science:

  • Immunology
  • Pulmonary Medicine
  • Microbiology

Background:

  • Secondary bacterial pneumonia, particularly from Staphylococcus aureus and Streptococcus pneumoniae, is a major complication of severe influenza.
  • The IL-22 pathway is crucial for lung host defense against these bacteria, but its regulation by IL-22-binding protein (IL-22BP) during super-infections is poorly understood.

Purpose of the Study:

  • To investigate the role of the IL-22/IL-22BP regulatory pathway in influenza and subsequent bacterial super-infection.
  • To determine the impact of IL-22BP deletion on host defense mechanisms and lung pathology during polymicrobial infection.

Main Methods:

  • Wild-type and IL-22BP knockout (IL-22BP-/-) mice were infected with influenza A virus, followed by challenge with Staphylococcus aureus and Streptococcus pneumoniae.
  • Bacterial burden, survival rates, inflammatory markers, lipocalin 2 expression, and epithelial barrier integrity (including tight junction stability) were assessed.
  • Human bronchial epithelial cells were used to evaluate the effect of IL-22Fc on tight junctions.

Main Results:

  • IL-22BP-/- mice exhibited significantly reduced bacterial burden and improved survival following influenza and bacterial super-infection compared to wild-type controls.
  • Deletion of IL-22BP led to decreased lung inflammation, increased lipocalin 2 expression, and preserved epithelial barrier function with enhanced tight junction stability.
  • In vitro studies showed that IL-22Fc treatment improved tight junction integrity in human bronchial epithelial cells.

Conclusions:

  • IL-22BP plays a detrimental role during influenza-induced bacterial super-infection, promoting inflammation and impairing epithelial barrier function.
  • Eliminating IL-22BP confers protection against severe outcomes of polymicrobial lung infections, highlighting its potential as a therapeutic target.
  • The IL-22/IL-22BP axis is a critical regulator of lung immunity and barrier homeostasis during complex respiratory infections.

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