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

Nat Commun. 2019 Apr 16;10(1):1780. 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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Animals
  • Blood Platelets / immunology*
  • Complement C3 / immunology
  • Complement C3 / metabolism
  • Disease Models, Animal
  • Extracellular Traps / immunology
  • Extracellular Traps / metabolism
  • Female
  • Humans
  • 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
  • Neutrophils / immunology
  • Platelet Activation / immunology*
  • Toll-Like Receptor 7 / genetics
  • Toll-Like Receptor 7 / immunology
  • Toll-Like Receptor 7 / metabolism


  • Complement C3
  • Membrane Glycoproteins
  • TLR7 protein, human
  • Tlr7 protein, mouse
  • Toll-Like Receptor 7