CD47 restricts antiviral function of alveolar macrophages during influenza virus infection

Christina Wenzek; Philine Steinbach; Florian Wirsdörfer; Kathrin Sutter; Julia D Boehme; Robert Geffers; Robert Klopfleisch; Dunja Bruder; Verena Jendrossek; Jan Buer; Astrid M Westendorf; Torben Knuschke

doi:10.1016/j.isci.2022.105540

CD47 restricts antiviral function of alveolar macrophages during influenza virus infection

iScience. 2022 Nov 11;25(12):105540. doi: 10.1016/j.isci.2022.105540. eCollection 2022 Dec 22.

Authors

Affiliations

¹ Institute of Medical Microbiology, University Hospital Essen, University of Duisburg-Essen, Essen 45147, Germany.
² Institute of Cell Biology (Cancer Research), University Hospital Essen, Essen 45147, Germany.
³ Institute for Virology, University Hospital Essen, University of Duisburg-Essen, Essen 45147, Germany.
⁴ Immune Regulation Group, Helmholtz Centre for Infection Research (HZI), Braunschweig 38124, Germany.
⁵ Infection Immunology Group, Institute of Medical Microbiology, Infection Control and Prevention, Health Campus Immunology, Infectiology and Inflammation, Otto-von-Guericke University, Magdeburg 39120, Germany.
⁶ Genome Analytics, Helmholtz Centre for Infection Research (HZI), Braunschweig 38124, Germany.
⁷ Institute of Veterinary Pathology, Freie Universitaet Berlin, Berlin 14163, 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.

Keywords: Immunology; Virology.