Inflammatory monocytes regulate Th1 oriented immunity to CpG adjuvanted protein vaccines through production of IL-12

Sci Rep. 2017 Jul 20;7(1):5986. doi: 10.1038/s41598-017-06236-6.

Abstract

Due to their capacity to skew T cell responses towards Th1 oriented immunity, oligonucleotides containing unmethylated CpG motifs (CpG) have emerged as interesting adjuvants for vaccination. Whereas the signalling pathways in response to CpG mediated TLR9 activation have been extensively documented at the level of the individual cell, little is however known on the precise identity of the innate immune cells that govern T cell priming and polarisation to CpG adjuvanted protein antigens in vivo. In this study, we demonstrate that optimal induction of Th1 oriented immunity to CpG adjuvanted protein vaccines requires the coordinated actions of conventional DCs and of monocytes. Whilst conventional DCs were required for antigen presentation and initial T cell priming, monocytes constitute the main source of the Th1 polarising cytokine IL-12.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adjuvants, Immunologic / pharmacology*
  • Animals
  • Antigen Presentation / drug effects
  • Antigen-Presenting Cells / drug effects
  • Antigen-Presenting Cells / metabolism
  • Antigens / metabolism
  • Antigens, Ly / metabolism
  • Cell Movement / drug effects
  • Dendritic Cells / drug effects
  • Dendritic Cells / metabolism
  • Immunity, Cellular* / drug effects
  • Inflammation / pathology*
  • Interleukin-12 / biosynthesis*
  • Lymph Nodes / drug effects
  • Lymph Nodes / metabolism
  • Lymph Nodes / pathology
  • Membrane Proteins / metabolism
  • Mice, Inbred C57BL
  • Monocytes / drug effects
  • Monocytes / metabolism
  • Monocytes / pathology*
  • Oligodeoxyribonucleotides / pharmacology*
  • Phenotype
  • Receptors, CCR2 / metabolism
  • Th1 Cells / immunology*
  • Vaccination
  • Vaccines / immunology*

Substances

  • Adjuvants, Immunologic
  • Antigens
  • Antigens, Ly
  • CPG-oligonucleotide
  • Ccr2 protein, mouse
  • Ly-6C antigen, mouse
  • Membrane Proteins
  • Oligodeoxyribonucleotides
  • Receptors, CCR2
  • Vaccines
  • flt3 ligand protein
  • Interleukin-12