TY - JOUR
T1 - Plasminogen Controls Inflammation and Pathogenesis of Influenza Virus Infections via Fibrinolysis
AU - Berri, F
AU - Rimmelzwaan, Guus
AU - Hanss, M
AU - Albina, E
AU - Foucault-Grunenwald, ML
AU - Le, VB
AU - Trierum, Stella
AU - Gil, P
AU - Camerer, E
AU - Martinez, D
AU - Lina, B
AU - Lijnen, R
AU - Carmeliet, P
AU - Riteau, B
PY - 2013
Y1 - 2013
N2 - 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.
AB - 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.
U2 - 10.1371/journal.ppat.1003229
DO - 10.1371/journal.ppat.1003229
M3 - Article
C2 - 23555246
SN - 1553-7366
VL - 9
JO - PLoS Pathogens (print)
JF - PLoS Pathogens (print)
IS - 3
ER -