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

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

Author information

1
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.
2
Virus et Immunité, Institut Pasteur URA CNRS 3015.
3
Régulation Immunitaire et Vaccinologie INSERM U1041.
4
Department of Obstetrics and Gynecology, Hopital Bichat Claude Bernard Paris 7 Diderot University.
5
APHP, Maternité Port Royal Université Paris Descartes, Sorbonne Paris Cité, Paris, France.
6
APHP, Hopital Cochin INSERM CIC1417 Université Paris Descartes, Sorbonne Paris Cité, Paris, France.

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.

KEYWORDS:

Influenza Vaccine; Newborn; Plasmacytoid dendritic cells; Th1

PMID:
24558121
DOI:
10.1093/infdis/jiu103
[Indexed for MEDLINE]
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