Abstract
Plasmacytoid dendritic cells (pDCs) are key players in the antiviral immune response and type III IFNs such as IL‐29 appear to play a pivotal role in pDC function. Pronounced susceptibility to viral infections in neonates is partly resulting from diminished antiviral immune mechanisms. Accordingly, the aim of the present study was to investigate the impact of IL‐29 in the altered immune response of neonatal pDCs. PBMCs of adult and term newborns were stimulated with CpG‐ODN2216 in the presence or absence of IL‐29 and assessed for IFN‐α production, downstream‐signaling, and activation marker expression. A significantly lower IL‐29 production after TLR9‐specific stimulation was demonstrated in neonatal pDCs. IL‐29 enhanced the IFN‐α production of pDCs in adults compared to newborns. Newborn pDCs displayed a significantly lower surface expression of IL‐10 and IL‐28Rα receptor resulting in diminished STAT1 and IRF7 activation. Interestingly, concomitant stimulation with CpG‐ODN2216/IL‐29 had no impact on the expression of surface activation and maturation markers of pDCs in neither population. The diminished antiviral immune response of neonatal pDCs is associated with reduced production and cellular responses toward IL‐29. Potential therapeutic agents enhancing the IL‐29 response in neonatal pDCs possibly augment viral protection in newborns.
Highlights
The susceptibility to infections of newborn infants partly results from a hyporesponsiveness of innate immune responses against bacterial and viral antigens
To determine the mechanism behind the diminished functional response against IL-29 of newborn plasmacytoid dendritic cell (pDC), we investigated the expression of surface receptors and associated signaling molecules of type I and III IFNs pathways
IL-29 exerts a variety of immunomodulatory effects on various cell types.[10,13,14,15]
Summary
The susceptibility to infections of newborn infants partly results from a hyporesponsiveness of innate immune responses against bacterial and viral antigens. This “immaturity” of neonatal immune responses is associated with neonatal morbidity and mortality.[1] In recent years, novel insights in immunological impairments of the neonatal immune system have been described, revealing diminished defending responses against infectious triggers.[2,3,4]. Plasmacytoid dendritic cells (pDCs) are rare peripheral blood cells, this small population of cells is a crucial player in the antiviral innate immune response, due to their ability to produce 100 times more type I IFNs than other cell types in response to viral antigens. Neonatal pDCs show a gestational-age dependent maturation of early antiviral immune responses after TLR engagement, they still display reduced responses when compared to healthy adults.[4,5] During the last decade, type III IFNs have been described as new IFN family members adding additional concepts to the complex
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