CD47 restricts antiviral function of alveolar macrophages during influenza virus infection

Christina Wenzek1, Philine Steinbach1, Florian Wirsdörfer2

  • 1Institute of Medical Microbiology, University Hospital Essen, University of Duisburg-Essen, Essen 45147, Germany.

Iscience
|November 28, 2022
PubMed

Insights

CD47 deficiency enhances viral clearance by boosting alveolar macrophage antiviral responses. This occurs because CD47 normally restricts hemoglobin expression, which is crucial for antiviral immunity.

Area of Science:

  • Immunology
  • Virology
  • Molecular Biology

Background:

  • CD47 is a cell surface molecule influencing immune responses.
  • The specific role of CD47 in antiviral immunity remains unclear.
  • Influenza A virus (IAV) and SARS-CoV-2 are significant respiratory pathogens.

Purpose of the Study:

  • To investigate the role of CD47 in antiviral immunity.
  • To determine how CD47 affects viral clearance during infection.
  • To elucidate the mechanism by which CD47 influences immune cell function.

Main Methods:

  • Utilized CD47-deficient (CD47-/-) mice and wildtype mice.
  • Infected mice with influenza A virus (IAV).
  • Depleted alveolar macrophages (aMФ) in CD47-/- mice during infection.
  • Measured viral clearance and assessed CD47 and hemoglobin (HB) expression in aMФ.
  • Investigated the impact of HB on IFN-β response.

Main Results:

  • CD47-/- mice exhibited enhanced clearance of IAV compared to wildtype mice.
  • Alveolar macrophages (aMФ) mediate this augmented viral clearance.
  • Depletion of aMФ in CD47-/- mice reversed the enhanced viral clearance.
  • CD47 restricts HB expression in aMФ following IAV and SARS-CoV-2 infection.
  • Hemoglobin (HB) enhances the antiviral interferon-beta (IFN-β) response.

Conclusions:

  • CD47 plays a negative role in antiviral immunity within the lung.
  • CD47 restricts the antiviral properties of hemoglobin in alveolar macrophages.
  • Targeting CD47 may represent a novel strategy for enhancing antiviral responses.