Influenza Vaccination Induces NK-Cell-Mediated Type-II IFN Response that Regulates Humoral Immunity in an IL-6-Dependent Manner

Cell Rep. 2019 Feb 26;26(9):2307-2315.e5. doi: 10.1016/j.celrep.2019.01.104.


The role of natural killer (NK) cells in the immune response against vaccines is not fully understood. Here, we examine the function of infiltrated NK cells in the initiation of the inflammatory response triggered by inactivated influenza virus vaccine in the draining lymph node (LN). We observed that, following vaccination, NK cells are recruited to the interfollicular and medullary areas of the LN and become activated by type I interferons (IFNs) produced by LN macrophages. The activation of NK cells leads to their early production of IFNγ, which in turn regulates the recruitment of IL-6+ CD11b+ dendritic cells. Finally, we demonstrate that the interleukin-6 (IL-6)-mediated inflammation is important for the development of an effective humoral response against influenza virus in the draining LN.

Keywords: IFNγ; IL-6; dendritic cell; influenza vaccine; natural killer cell; type I IFN.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cells, Cultured
  • Female
  • Immunity, Humoral*
  • Inflammation / immunology
  • Influenza Vaccines / immunology*
  • Interferon Type I / physiology
  • Interferon-gamma / metabolism*
  • Interleukin-6 / biosynthesis*
  • Interleukin-6 / physiology
  • Killer Cells, Natural / immunology*
  • Lymph Nodes / immunology
  • Macrophages / immunology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout


  • Influenza Vaccines
  • Interferon Type I
  • Interleukin-6
  • interleukin-6, mouse
  • Interferon-gamma