Plasminogen Controls Inflammation and Pathogenesis of Influenza Virus Infections via Fibrinolysis

Abstract

Detrimental inflammation of the lungs is a hallmark of severe influenza virus infections. Endothelial cells are the source of cytokine amplification, although mechanisms underlying this process are unknown. Here, using combined pharmacological and gene-deletion approaches, we show that plasminogen controls lung inflammation and pathogenesis of infections with influenza A/PR/8/34, highly pathogenic H5N1 and 2009 pandemic H1N1 viruses. Reduction of virus replication was not responsible for the observed effect. However, pharmacological depletion of fibrinogen, the main target of plasminogen reversed disease resistance of plasminogen-deficient mice or mice treated with an inhibitor of plasminogen-mediated fibrinolysis. Therefore, plasminogen contributes to the deleterious inflammation of the lungs and local fibrin clot formation may be implicated in host defense against influenza virus infections. Our studies suggest that the hemostatic system might be explored for novel treatments against influenza.

Keywords

Affiliated Institutions

• Université Paris Cité FR
• Vlaams Instituut voor Biotechnologie BE
• Virologie et Pathologies Humaines FR
• UCLouvain BE
• Hospices Civils de Lyon FR
• Délégation Paris 5 FR
• Paris Cardiovascular Research Center FR
• Département Santé Animale FR
• Université Claude Bernard Lyon 1 FR
• Centre de Recherche et de Veille sur les Maladies Emergentes dans l’Océan Indien FR

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