Macrophage Death following Influenza Vaccination Initiates the Inflammatory Response that Promotes Dendritic Cell Function in the Draining Lymph Node

Cell Rep. 2017 Mar 7;18(10):2427-2440. doi: 10.1016/j.celrep.2017.02.026.


The mechanism by which inflammation influences the adaptive response to vaccines is not fully understood. Here, we examine the role of lymph node macrophages (LNMs) in the induction of the cytokine storm triggered by inactivated influenza virus vaccine. Following vaccination, LNMs undergo inflammasome-independent necrosis-like death that is reliant on MyD88 and Toll-like receptor 7 (TLR7) expression and releases pre-stored interleukin-1α (IL-1α). Furthermore, activated medullary macrophages produce interferon-β (IFN-β) that induces the autocrine secretion of IL-1α. We also found that macrophage depletion promotes lymph node-resident dendritic cell (LNDC) relocation and affects the capacity of CD11b+ LNDCs to capture virus and express co-stimulatory molecules. Inhibition of the IL-1α-induced inflammatory cascade reduced B cell responses, while co-administration of recombinant IL-1α increased the humoral response. Stimulation of the IL-1α inflammatory pathway might therefore represent a strategy to enhance antigen presentation by LNDCs and improve the humoral response against influenza vaccines.

Keywords: CD11b(+) DC; IFN-β; IL-1α; MCP-1; alarmin; cytokine storm; inflammatory cascade; influenza; lymph node macrophages; vaccine.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigen Presentation / immunology
  • Cell Death
  • Cell Movement
  • Dendritic Cells / immunology*
  • Immunity, Humoral
  • Inflammation / pathology*
  • Influenza Vaccines / administration & dosage
  • Influenza Vaccines / immunology*
  • Interferon-beta / metabolism
  • Interleukin-1alpha / metabolism
  • Lymph Nodes / immunology*
  • Macrophage Activation
  • Macrophages / pathology*
  • Macrophages / virology*
  • Mice, Inbred C57BL
  • Myeloid Differentiation Factor 88 / metabolism
  • Orthomyxoviridae Infections / immunology*
  • Orthomyxoviridae Infections / virology
  • Toll-Like Receptor 7 / metabolism
  • Vaccination*
  • Virus Internalization


  • Influenza Vaccines
  • Interleukin-1alpha
  • Myeloid Differentiation Factor 88
  • Toll-Like Receptor 7
  • Interferon-beta