title: Plasmacytoid dendritic cells engagement by influenza vaccine as a surrogate strategy for driving T-helper type 1 responses in human neonatal settings.
abstract: 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.
authors.affiliation: Régulation Immunitaire et Vaccinologie INSERM U1041 Unit of Innate Defense and Immune Modulation, Key Laboratory of Molecular Virology and Immunology, Institut Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai, China.
authors.forename: Xiaoming
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Virus et Immunité, Institut Pasteur URA CNRS 3015.
authors.forename: Nicoletta
authors.initials: N
authors.lastname: Casartelli
authors.affiliation: Régulation Immunitaire et Vaccinologie INSERM U1041.
authors.forename: Sebastien
authors.initials: S
authors.lastname: Lemoine
authors.affiliation: Régulation Immunitaire et Vaccinologie INSERM U1041.
authors.forename: Brian
authors.initials: B
authors.lastname: Mozeleski
authors.affiliation: Department of Obstetrics and Gynecology, Hopital Bichat Claude Bernard Paris 7 Diderot University.
authors.forename: Elie
authors.initials: E
authors.lastname: Azria
authors.affiliation: APHP, Maternité Port Royal Université Paris Descartes, Sorbonne Paris Cité, Paris, France.
authors.forename: Camille
authors.initials: C
authors.lastname: Le Ray
authors.affiliation: Virus et Immunité, Institut Pasteur URA CNRS 3015.
authors.forename: Olivier
authors.initials: O
authors.lastname: Schwartz
authors.affiliation: APHP, Hopital Cochin INSERM CIC1417 Université Paris Descartes, Sorbonne Paris Cité, Paris, France.
authors.forename: Odile
authors.initials: O
authors.lastname: Launay
authors.affiliation: Régulation Immunitaire et Vaccinologie INSERM U1041.
authors.forename: Claude
authors.initials: C
authors.lastname: Leclerc
authors.affiliation: Régulation Immunitaire et Vaccinologie INSERM U1041.
authors.forename: Richard
authors.initials: R
authors.lastname: Lo-Man
mesh_terms: D000375:Aging; D003713:Dendritic Cells / Q000502:physiology*; D005312:Fetal Blood / Q000166:cytology; D006801:Humans; D007115:Immunization Schedule; D007231:Infant, Newborn; D007252:Influenza Vaccines / Q000276:immunology*; D016898:Interferon-alpha / Q000235:genetics / Q000378:metabolism; D007371:Interferon-gamma / Q000235:genetics / Q000378:metabolism; D018664:Interleukin-12 / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D006377:T-Lymphocytes, Helper-Inducer / Q000145:classification* / Q000502:physiology*; D018417:Th1 Cells / Q000502:physiology; D014611:Vaccination
chemical_list: D007252:Influenza Vaccines; D016898:Interferon-alpha; D018664:Interleukin-12; D007371:Interferon-gamma
keywords: Influenza Vaccine; Newborn; Plasmacytoid dendritic cells; Th1