Plasmacytoid Dendritic Cells Engagement by Influenza Vaccine as a Surrogate Strategy for Driving T-Helper Type 1 Responses in Human Neonatal Settings. (20th February 2014)

• Record Type: Journal Article
• Authors: Zhang, Xiaoming; Casartelli, Nicoletta; Lemoine, Sebastien; Mozeleski, Brian; Azria, Elie; Le Ray, Camille; Schwartz, Olivier; Launay, Odile; Leclerc, Claude; Lo-Man, Richard
• Is Part Of: Journal of infectious diseases. Volume 210(2014)Supplement 3
• Page Start: 424
• Page End: 434
• Publication Date: 2014-02-20
• Subjects: Plasmacytoid dendritic cells -- Newborn -- Th1 -- Influenza Vaccine; Communicable diseases -- Periodicals; Diseases -- Causes and theories of causation -- Periodicals; Medicine -- Periodicals; Communicable Diseases -- Periodicals; Electronic journals; 616.9
• DOI: 10.1093/infdis/jiu103
• Languages: English
• ISSNs: 0022-1899

Abstract

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.