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Xiaoming Zhang, Nicoletta Casartelli, Sebastien Lemoine, Brian Mozeleski, Elie Azria, Camille Le Ray, Olivier Schwartz, Odile Launay, Claude Leclerc, Richard Lo-Man, Plasmacytoid Dendritic Cells Engagement by Influenza Vaccine as a Surrogate Strategy for Driving T-Helper Type 1 Responses in Human Neonatal Settings, The Journal of Infectious Diseases, Volume 210, Issue 3, 1 August 2014, Pages 424–434, https://doi.org/10.1093/infdis/jiu103
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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.