title: Influenza virus H1N1 activates platelets through FcγRIIA signaling and thrombin generation.
abstract: Platelets play crucial functions in hemostasis and the prevention of bleeding. 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 the H1N1 pandemic were reported to play a pathogenic role, we assessed their contribution in H1N1-induced platelet activation. In influenza-immunized subjects, we observed that the virus scaffolds with immunoglobulin G (IgG) to form immune complexes that promote platelet activation. Mechanistically, this activation occurs through stimulation of low-affinity type 2 receptor for Fc portion of IgG (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 the 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 2 intertwined processes that activate platelets during influenza infections.
authors.affiliation: Axe des Maladies Infectieuses et Immunitaires, Centre de Recherche du Centre Hospitalier Universitaire de Québec and Faculté de Médecine de l'Université Laval, Quebec City, QC, Canada.
authors.forename: Eric
authors.initials: E
authors.lastname: Boilard
authors.forename: Guillaume
authors.initials: G
authors.lastname: Paré
authors.forename: Matthieu
authors.initials: M
authors.lastname: Rousseau
authors.forename: Nathalie
authors.initials: N
authors.lastname: Cloutier
authors.forename: Isabelle
authors.initials: I
authors.lastname: Dubuc
authors.forename: Tania
authors.initials: T
authors.lastname: Lévesque
authors.forename: Pierre
authors.initials: P
authors.lastname: Borgeat
authors.forename: Louis
authors.initials: L
authors.lastname: Flamand
mesh_terms: D000818:Animals; D000914:Antibodies, Viral / Q000276:immunology; D000936:Antigen-Antibody Complex / Q000276:immunology; D001792:Blood Platelets / Q000276:immunology* / Q000378:metabolism*; D006801:Humans; D007113:Immunity, Innate; D016130:Immunophenotyping; D053118:Influenza A Virus, H1N1 Subtype / Q000276:immunology*; D051379:Mice; D008822:Mice, Transgenic; D009976:Orthomyxoviridae Infections / Q000276:immunology / Q000378:metabolism; D010641:Phenotype; D015539:Platelet Activation / Q000276:immunology*; D017452:Receptors, IgG / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D013917:Thrombin / Q000378:metabolism*
chemical_list: D000914:Antibodies, Viral; D000936:Antigen-Antibody Complex; C080568:Fc gamma receptor IIA; D017452:Receptors, IgG; D013917:Thrombin