Novel protective mechanism for interleukin-33 at the mucosal barrier during influenza-associated bacterial

K M Robinson1, K Ramanan2, M E Clay2,3

  • 1Department of Medicine, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA.

Mucosal Immunology
|April 13, 2017
PubMed

Insights

Influenza A virus impairs the immune response, increasing susceptibility to bacterial pneumonia. Restoring interleukin-33 (IL-33) enhances bacterial clearance and survival during superinfections.

Area of Science:

  • Immunology
  • Microbiology
  • Infectious Diseases

Background:

  • Influenza A virus infections can lead to severe bacterial superinfections, a major cause of mortality.
  • Influenza impairs host defense mechanisms, increasing vulnerability to secondary bacterial pneumonia.

Purpose of the Study:

  • To investigate the role of interleukin-33 (IL-33) in host defense during influenza and bacterial superinfection.
  • To determine if restoring IL-33 levels can mitigate the effects of superinfection and improve outcomes.

Main Methods:

  • Studied the effect of influenza A infection on Staphylococcus aureus-induced IL-33 production in a model system.
  • Administered IL-33 during coinfection with influenza A and methicillin-resistant S. aureus.
  • Assessed bacterial clearance, mortality rates, and immune cell recruitment (neutrophils) in the lungs.

Main Results:

  • Influenza A infection was found to inhibit Staphylococcus aureus-induced IL-33 production.
  • Restoration of IL-33 significantly enhanced bacterial clearance and improved survival rates during coinfection.
  • IL-33 treatment promoted neutrophil recruitment to the lungs, correlating with improved bacterial clearance.
  • IL-33-mediated protection was independent of Innate lymphoid Type 2 cells and alternatively activated macrophages.

Conclusions:

  • Interleukin-33 plays a critical role in antibacterial host defense at the mucosal barrier during influenza superinfections.
  • Targeting IL-33 represents a potential therapeutic strategy to combat severe outcomes of influenza-associated bacterial pneumonia.

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