CD47 restricts antiviral function of alveolar macrophages during influenza virus infection

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 (aM Phi). Although aM Phi displayed upregulation of CD47 expression during IAV infection in wildtype mice, depletion of aM Phi in CD47(-/- )mice during IAV infection reversed the augmented viral clearance. We have also demonstrated that CD47 restricts hemoglobin (HB) expression in aM Phi after IAV and severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) infection, with HB showing anti-viral properties by enhancing the IFN-b response. Our study showed a negative role for CD47 during antiviral immune responses in the lung by confining HB expression in aM Phi.

Automated summary

CD47 plays a significant role in immune responses, but its role in antiviral immunity is not fully understood. This study revealed that CD47-deficient mice showed enhanced clearance of IAV, and this enhanced clearance was mediated by aM Phi. The study also found that CD47 restricts HB expression in aM Phi after IAV and SARS-CoV-2 infection, and HB enhances the IFN-b response, showing antiviral properties.