Neonatal Plasmacytoid Dendritic Cells (pDCs) Display Subset Variation but Can Elicit Potent Anti-Viral Innate Responses

Xiaoming Zhang,Elie Azria,Richard Lo-Man,Olivier Schwartz,Alice Lepelley,Pierre Lebon,Odile Launay,Claude Leclerc,Gwenaelle Roguet

doi:10.1371/journal.pone.0052003

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.

Highlights

How the immune system in early infancy accommodates pathogens is poorly defined and requires assessment to contrive and improve treatments and vaccines [1]
Neonatal pDCs were shown to be defective for IFN-a response to CpG/TLR9 activation, but these early studies were performed with pDCs of 50% purity [14]. pDCs can be clearly identified by the expression of BDCA4 and BDCA2, as well as the high expression of CD45RA and CD123
We further investigated functions of cord blood pDCs to .99% purity by magnetic bead enrichement of BDCA4 cells followed by FACS sorting on CD123 and CD45RA expression (Fig. S1) and exposed these cells to viruses. pDCs purified from adult and neonatal blood responded (Fig. 1A)

Summary

Introduction

How the immune system in early infancy accommodates pathogens is poorly defined and requires assessment to contrive and improve treatments and vaccines [1]. We first sought to analyze the antiviral IFN-a response of cord blood cells to TLR7 dependent IAV [16] and HIV [17] as well as in response to TLR9 dependent HSV [18] and CpGA activation (Fig. 1). Neonatal pDCs were shown to be defective for IFN-a response to CpG/TLR9 activation, but these early studies were performed with pDCs of 50% purity [14].

Results

Conclusion