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Isolation and In Vitro Culture of Murine and Human Alveolar Macrophages
Published on: April 20, 2018
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.
Abstract:
CD47 is an ubiquitously expressed surface molecule with significant impact on immune responses. However, its role for antiviral immunity is not fully understood. Here, we revealed that the expression of CD47 on immune cells seemed to disturb the antiviral immune response as CD47-deficient mice (CD47-/-) showed an augmented clearance of influenza A virus (IAV). Specifically, we have shown that enhanced viral clearance is mediated by alveolar macrophages (aMФ). Although aMФ displayed upregulation of CD47 expression during IAV infection in wildtype mice, depletion of aMФ in CD47-/- mice during IAV infection reversed the augmented viral clearance. We have also demonstrated that CD47 restricts hemoglobin (HB) expression in aMФ after IAV and severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) infection, with HB showing antiviral properties by enhancing the IFN-β response. Our study showed a negative role for CD47 during antiviral immune responses in the lung by confining HB expression in aMФ.
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.
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