Abstract
BackgroundCharacteristics of the human neonatal immune system are thought to be responsible for heightened susceptibility to infectious pathogens and poor responses to vaccine antigens. Using cord blood as a source of immune cells, many reports indicate that the response of neonatal monocytes and dendritic cells (DC) to Toll-like receptor (TLR) agonists differs significantly from that of adult cells. Herein, we analyzed the evolution of these responses within the first year of life.Methodology/Principal FindingsBlood samples from children (0, 3, 6, 9, 12 month old) and healthy adults were stimulated ex vivo with bacterial lipopolysaccharide (LPS, TLR4 agonist) or CpG oligonucleotides (TLR9 agonist). We determined phenotypic maturation of monocytes, myeloid (m) and plasmacytoid (p) DC and production of cytokines in the culture supernatants. We observed that surface expression of CD80 and HLA-DR reaches adult levels within the first 3 months of life for mDCs and 6–9 months of life for monocytes and pDCs. In response to LPS, production of TNF-α, IP-10 and IL-12p70 reached adult levels between 6–9 months of life. In response to CpG stimulation, production of type I IFN-dependent chemokines (IP-10 and CXCL9) gradually increased with age but was still limited in 1-year old infants as compared to adult controls. Finally, cord blood samples stimulated with CpG ODN produced large amounts of IL-6, IL-8, IL-1β and IL-10, a situation that was not observed for 3 month-old infants.ConclusionsThe first year of life represents a critical period during which adult-like levels of TLR responses are reached for most but not all cytokine responses.
Highlights
The characteristics of immune responses in early life are often held responsible for heightened sensitivity towards infectious agents and suboptimal responses to vaccination [1,2]
It has long been noted that production of IL-10 is elevated in LPS-stimulated cord blood in comparison to adult samples, which can down-modulate the production of other cytokines [8,9]
Using 6-color flow cytometry, we analyzed the expression of CD80 and HLA DR molecules at the surface of monocytes (Lin, CD14+, CD11c+), mDCs (Lin, CD14, CD11c+, CD123-) and Plasmacytoid DCs (pDCs) (Lin, CD14, CD11c, CD123+)
Summary
The characteristics of immune responses in early life are often held responsible for heightened sensitivity towards infectious agents and suboptimal responses to vaccination [1,2]. The capacity of neonatal monocytes and dendritic cells (DC) to produce cytokines in response to Toll-like receptor (TLR) agonists differs significantly from that of adult cells. Several reports have noted that production of TNF-a is impaired in early life. This defect is observed only in certain experimental conditions. Using cord blood as a source of immune cells, many reports indicate that the response of neonatal monocytes and dendritic cells (DC) to Toll-like receptor (TLR) agonists differs significantly from that of adult cells. We analyzed the evolution of these responses within the first year of life
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