IL-1R signaling in dendritic cells replaces pattern-recognition receptors in promoting CD8⁺ T cell responses to influenza A virus

Nat Immunol. 2013 Mar;14(3):246-53. doi: 10.1038/ni.2514. Epub 2013 Jan 13.

Abstract

Immune responses to vaccines require direct recognition of pathogen-associated molecular patterns (PAMPs) through pattern-recognition receptors (PRRs) on dendritic cells (DCs). Unlike vaccination, infection by a live pathogen often impairs DC function and inflicts additional damage on the host. Here we found that after infection with live influenza A virus, signaling through the interleukin 1 receptor (IL-1R) was required for productive priming of CD8(+) T cells, but signaling through the PRRs TLR7 and RIG-I was not. DCs activated by IL-1 in trans were both required and sufficient for the generation of virus-specific CD8(+) T cell immunity. Our data demonstrate a critical role for a bystander cytokine in the priming of CD8(+) T cells during infection with a live virus.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • CD8-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / virology
  • Cell Differentiation
  • Cell Movement
  • Dendritic Cells / immunology*
  • Dendritic Cells / metabolism
  • Dendritic Cells / virology
  • Influenza A virus / immunology*
  • Interleukin-1 / immunology
  • Lymphocyte Activation
  • Membrane Glycoproteins / metabolism
  • Membrane Proteins / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Myeloid Differentiation Factor 88 / metabolism
  • Nerve Tissue Proteins / metabolism
  • Orthomyxoviridae Infections / immunology
  • Receptors, CCR7 / biosynthesis
  • Receptors, Cell Surface
  • Receptors, Interleukin-1 / genetics
  • Receptors, Interleukin-1 / metabolism*
  • Receptors, Pattern Recognition / immunology
  • Receptors, Pattern Recognition / metabolism*
  • Signal Transduction
  • Toll-Like Receptor 7 / metabolism

Substances

  • Ccr7 protein, mouse
  • Interleukin-1
  • Membrane Glycoproteins
  • Membrane Proteins
  • Myd88 protein, mouse
  • Myeloid Differentiation Factor 88
  • Nerve Tissue Proteins
  • Receptors, CCR7
  • Receptors, Cell Surface
  • Receptors, Interleukin-1
  • Receptors, Pattern Recognition
  • Robo3 protein, mouse
  • Tlr7 protein, mouse
  • Toll-Like Receptor 7