Monocyte-derived dendritic cells enhance protection against secondary influenza challenge by controlling the switch in CD8+ T-cell immunodominance

Eur J Immunol. 2017 Feb;47(2):345-352. doi: 10.1002/eji.201646523. Epub 2016 Dec 9.

Abstract

Influenza virus infection triggers an increase in the number of monocyte-derived dendritic cells (moDCs) in the respiratory tract, but the role of these cells during antiviral immunity is still unclear. Here we show that during influenza infection, moDCs dominate the late activation of CD8+ T cells and trigger the switch in immunodominance of the CD8+ T-cell response from acidic polymerase specificity to nucleoprotein specificity. Abrogation of monocyte recruitment or depletion of moDCs strongly compromised host resistance to secondary influenza challenge. These findings underscore a novel function of moDCs in the antiviral response to influenza virus, and have important implications for vaccine design.

Keywords: CD8+ T cell · Dendritic cell · Immunodominance · Influenza virus · Monocyte.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CD8-Positive T-Lymphocytes / immunology*
  • Cells, Cultured
  • Dendritic Cells / immunology*
  • Dendritic Cells / virology
  • Immunodominant Epitopes / immunology
  • Immunologic Memory
  • Influenza A Virus, H1N1 Subtype / immunology*
  • Lung / immunology*
  • Lung / virology
  • Lymphocyte Activation
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mice, Transgenic
  • Monocytes / immunology*
  • Orthomyxoviridae Infections / immunology*
  • T-Cell Antigen Receptor Specificity*
  • Viral Core Proteins / immunology

Substances

  • Immunodominant Epitopes
  • Viral Core Proteins