Plasmacytoid dendritic cells engagement by influenza vaccine as a surrogate strategy for driving T-helper type 1 responses in human neonatal settings

J Infect Dis. 2014 Aug 1;210(3):424-34. doi: 10.1093/infdis/jiu103. Epub 2014 Feb 20.


Background: The elicitation of T-helper type 1 (Th1) cellular immunity to eradicate intracellular pathogens is a challenging task because of the interleukin 12 (IL-12) deficit observed in early infancy.

Methods: Screening cord blood responses to various pediatric vaccines and Toll-like receptor (TLR) agonists for innate responses and CD4(+) T-cell differentiation.

Results: We identified that nonadjuvanted inactivated trivalent influenza vaccine (TIV) was able to cosignal T cells for the production of interferon γ (IFN-γ) in a neonatal setting. This process includes the mobilization of neonatal plasmacytoid dendritic cells (pDCs) as antigen-presenting cells (APCs) that efficiently engage Th1 cells in an IL-12-independent but type I IFN-dependent manner. In addition, cord blood pDCs efficiently cross-presented antigen to CD8(+) T cells. Importantly, activation by TIV mainly requires TLR7; however, R848/TLR7- and CpGB/TLR9-activated pDCs, which poorly produced IFN-α, induce neonatal Th2 responses.

Conclusions: TLR pathway engagement in pDCs is necessary but not sufficient for a successful neonatal Th1 outcome. We provide evidence of a mature and functional neonatal immune system at the level of APCs and T cells and propose to implement the IFN-α/IFN-γ axis in pediatric vaccination as a surrogate for the defective IL-12/IFN-γ axis.

Keywords: Influenza Vaccine; Newborn; Plasmacytoid dendritic cells; Th1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aging
  • Dendritic Cells / physiology*
  • Fetal Blood / cytology
  • Humans
  • Immunization Schedule
  • Infant, Newborn
  • Influenza Vaccines / immunology*
  • Interferon-alpha / genetics
  • Interferon-alpha / metabolism
  • Interferon-gamma / genetics
  • Interferon-gamma / metabolism
  • Interleukin-12 / genetics
  • Interleukin-12 / metabolism
  • Signal Transduction
  • T-Lymphocytes, Helper-Inducer / classification*
  • T-Lymphocytes, Helper-Inducer / physiology*
  • Th1 Cells / physiology
  • Vaccination


  • Influenza Vaccines
  • Interferon-alpha
  • Interleukin-12
  • Interferon-gamma