Neonatal plasmacytoid dendritic cells (pDCs) display subset variation but can elicit potent anti-viral innate responses

PLoS One. 2013;8(1):e52003. doi: 10.1371/journal.pone.0052003. Epub 2013 Jan 10.

Abstract

Neonates are highly susceptible to infectious diseases and defective antiviral pDC immune responses have been proposed to contribute to this phenomenon. Isolated cord blood pDCs innately responded to a variety of TLR7 and TLR9 dependent viruses, including influenza A virus (IAV), human immunodeficiency virus (HIV) or herpes-simplex virus (HSV) by efficiently producing IFN-α, TNF-α as well as chemokines. Interestingly, following activation by CpGA, but not viruses, cord pDCs tend to survive less efficiently. We found that a hallmark of pDCs in neonates is an extended CD2+pDCs compartment compared to adult pDCs without affecting the antiviral IFN-α response. Within CD2+pDCs, we identified a subpopulation expressing CD5 and responsible for IL-12p40 production, however this population is significantly decreased in cord blood compared to adult blood. Therefore, neonatal pDCs clearly display variation in phenotype and subset composition, but without major consequences for their antiviral responses.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • CD2 Antigens / immunology
  • CD2 Antigens / metabolism
  • CD5 Antigens / immunology
  • CD5 Antigens / metabolism
  • Cells, Cultured
  • Chemokines / immunology*
  • Chemokines / metabolism
  • Dendritic Cells / immunology*
  • Dendritic Cells / metabolism
  • Dendritic Cells / virology
  • Flow Cytometry
  • Humans
  • Immunity, Innate / drug effects
  • Immunity, Innate / immunology
  • Infant, Newborn
  • Interferon-alpha / immunology*
  • Interferon-alpha / metabolism
  • Interleukin-12 Subunit p40 / immunology
  • Interleukin-12 Subunit p40 / metabolism
  • Middle Aged
  • Oligodeoxyribonucleotides / immunology
  • Oligodeoxyribonucleotides / pharmacology
  • Toll-Like Receptor 7 / immunology
  • Toll-Like Receptor 7 / metabolism
  • Toll-Like Receptor 9 / immunology
  • Toll-Like Receptor 9 / metabolism
  • Tumor Necrosis Factor-alpha / immunology*
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • CD2 Antigens
  • CD5 Antigens
  • Chemokines
  • Interferon-alpha
  • Interleukin-12 Subunit p40
  • Oligodeoxyribonucleotides
  • TLR7 protein, human
  • Toll-Like Receptor 7
  • Toll-Like Receptor 9
  • Tumor Necrosis Factor-alpha

Grant support

This work was supported by grants from Agence Nationale pour la Recherche (ANR 09-MIEN-017) and has received funding from the French Government's Investissement d'Avenir program, Laboratoire d'Excellence “Integrative Biology of Emerging Infectious Diseases” (grant n°ANR-10-LABX-62-IBEID)). Work in the O.S. lab is also supported by ANRS, Sidaction and Areva Foundation. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.