The role of platelets in mediating a response to human influenza infection

• Published in: Nature communications 2019-04, Vol.10 (1), p.1780-1780, Article 1780
• Main Authors: Koupenova, Milka, Corkrey, Heather A., Vitseva, Olga, Manni, Giorgia, Pang, Catherine J., Clancy, Lauren, Yao, Chen, Rade, Jeffrey, Levy, Daniel, Wang, Jennifer P., Finberg, Robert W., Kurt-Jones, Evelyn A., Freedman, Jane E.
• Format: Article
• Language: English
• Subjects: 13/21; 14/19; 14/28; 631/250/232/2051/1339; 631/250/2504/223/1699; 631/326/596/1578; 64/60; 692/308/575; Adult; Aged; Aged, 80 and over; Animal models; Animals; Blood; Blood Platelets - immunology; Complement C3 - immunology; Complement C3 - metabolism; Complement component C3; Deoxyribonucleic acid; Depletion; Disease Models, Animal; DNA; Extracellular Traps - immunology; Extracellular Traps - metabolism; Female; Human behavior; Humanities and Social Sciences; Humans; Immunomodulation; Infections; Influenza; Influenza A; Influenza A virus - immunology; Influenza A virus - isolation & purification; Influenza, Human - blood; Influenza, Human - immunology; Influenza, Human - virology; Male; Membrane Glycoproteins - genetics; Membrane Glycoproteins - immunology; Membrane Glycoproteins - metabolism; Mice, Inbred C57BL; Mice, Knockout; Middle Aged; multidisciplinary; Myocardial infarction; Neutrophils; Neutrophils - immunology; Occlusion; Platelet Activation - immunology; Platelets; Science; Science (multidisciplinary); TLR7 protein; Toll-Like Receptor 7 - genetics; Toll-Like Receptor 7 - immunology; Toll-Like Receptor 7 - metabolism; Toll-like receptors; Vascular occlusion; Viruses
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-019-09607-x

Influenza infection increases the incidence of myocardial infarction but the reason is unknown. Platelets mediate vascular occlusion through thrombotic functions but are also recognized to have immunomodulatory activity. To determine if platelet processes are activated during influenza infection, we collected blood from 18 patients with acute influenza infection. Microscopy reveals activated platelets, many containing viral particles and extracellular-DNA associated with platelets. To understand the mechanism, we isolate human platelets and treat them with influenza A virus. Viral-engulfment leads to C3 release from platelets as a function of TLR7 and C3 leads to neutrophil-DNA release and aggregation. TLR7 specificity is confirmed in murine models lacking the receptor, and platelet depletion models support platelet-mediated C3 and neutrophil-DNA release post-influenza infection. These findings demonstrate that the initial intrinsic defense against influenza is mediated by platelet–neutrophil cross-communication that tightly regulates host immune and complement responses but can also lead to thrombotic vascular occlusion. Influenza viremia is rare in human blood and not well studied. Here, the authors show that influenza can be found in human platelets and that platelet engulfment of influenza A results in TLR7-dependent C3 release, which in turn promotes neutrophil-DNA release and formation of platelet-DNA aggregates.