tetano
Editor, Senior Moderator
Published online before print March 24, 2014, doi: 10.1182/blood-2013-07-515536
Submitted: July 16, 2013 Accepted: March 18, 2014
Influenza virus H1N1 activates platelets through FcγRIIA signaling and thrombin generation
Eric Boilard*,
Guillaume Par?,
Matthieu Rousseau,
Nathalie Cloutier,
Isabelle Dubuc,
Tania L?vesque,
Pierre Borgeat, and
Louis Flamand
1 Centre de Recherche en Rhumatologie et Immunologie, Centre de Recherche du Centre Hospitalier Universitaire de Quebec, Universite Laval, Quebec City, QC, Canada
↵* Corresponding author; email: eric.boilard{at}crchuq.ulaval.ca
Key points
In influenza-immune subjects, H1N1 influenza virus containing immune complexes can activate platelets through FcγRIIA.
H1N1 can also activate platelets through thrombin, independently of FcγRIIA, pointing to a role of coagulation in influenza infection.
Abstract
Platelets play crucial functions in haemostasis and the prevention of bleedings. During H1N1 influenza A virus infection, platelets display activation markers. The platelet activation triggers during H1N1 infection remain elusive. We observed that H1N1 induces surface receptor activation, lipid mediator synthesis and release of microparticles from platelets. These activation processes require the presence of serum/plasma, pointing to the contribution of soluble factor(s). Considering that immune complexes in H1N1 pandemic were reported playing a pathogenic role, we assessed their contribution in H1N1-induced platelet activation. In influenza-immunized subjects, we observed that the virus scaffolds with immunoglobulins G to form immune complexes that promote platelet activation. Mechanistically, this activation occurs through stimulation of FcγRIIA, a receptor for immune complexes, independently of thrombin. Using a combination of in vitro and in vivo approaches, we found that the antibodies from H3N2-immunized mice activate transgenic mouse platelets that express FcγRIIA when put in presence of H1N1, suggesting that cross-reacting influenza antibodies suffice. Alternatively, H1N1 can activate platelets via thrombin formation, independently of complement and FcγRIIA. These observations identify both the adaptive immune response and the innate response against pathogens as two intertwined processes that activate platelets during influenza infections.
http://bloodjournal.hematologylibrary.org/content/early/2014/03/24/blood-2013-07-515536.abstract
Submitted: July 16, 2013 Accepted: March 18, 2014
Influenza virus H1N1 activates platelets through FcγRIIA signaling and thrombin generation
Eric Boilard*,
Guillaume Par?,
Matthieu Rousseau,
Nathalie Cloutier,
Isabelle Dubuc,
Tania L?vesque,
Pierre Borgeat, and
Louis Flamand
1 Centre de Recherche en Rhumatologie et Immunologie, Centre de Recherche du Centre Hospitalier Universitaire de Quebec, Universite Laval, Quebec City, QC, Canada
↵* Corresponding author; email: eric.boilard{at}crchuq.ulaval.ca
Key points
In influenza-immune subjects, H1N1 influenza virus containing immune complexes can activate platelets through FcγRIIA.
H1N1 can also activate platelets through thrombin, independently of FcγRIIA, pointing to a role of coagulation in influenza infection.
Abstract
Platelets play crucial functions in haemostasis and the prevention of bleedings. During H1N1 influenza A virus infection, platelets display activation markers. The platelet activation triggers during H1N1 infection remain elusive. We observed that H1N1 induces surface receptor activation, lipid mediator synthesis and release of microparticles from platelets. These activation processes require the presence of serum/plasma, pointing to the contribution of soluble factor(s). Considering that immune complexes in H1N1 pandemic were reported playing a pathogenic role, we assessed their contribution in H1N1-induced platelet activation. In influenza-immunized subjects, we observed that the virus scaffolds with immunoglobulins G to form immune complexes that promote platelet activation. Mechanistically, this activation occurs through stimulation of FcγRIIA, a receptor for immune complexes, independently of thrombin. Using a combination of in vitro and in vivo approaches, we found that the antibodies from H3N2-immunized mice activate transgenic mouse platelets that express FcγRIIA when put in presence of H1N1, suggesting that cross-reacting influenza antibodies suffice. Alternatively, H1N1 can activate platelets via thrombin formation, independently of complement and FcγRIIA. These observations identify both the adaptive immune response and the innate response against pathogens as two intertwined processes that activate platelets during influenza infections.
http://bloodjournal.hematologylibrary.org/content/early/2014/03/24/blood-2013-07-515536.abstract