title: Acquisition of adult-like TLR4 and TLR9 responses during the first year of life.
abstract: BACKGROUND
  Characteristics 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.
  
  
  RESULTS
  Blood 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-alpha, 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-1beta and IL-10, a situation that was not observed for 3 month-old infants.
  
  
  CONCLUSIONS
  The 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.
authors.affiliation: Institute for Medical Immunology, Université Libre de Bruxelles, Gosselies, Belgium.
authors.forename: Muriel
authors.initials: M
authors.lastname: Nguyen
authors.forename: Elke
authors.initials: E
authors.lastname: Leuridan
authors.forename: Tong
authors.initials: T
authors.lastname: Zhang
authors.forename: Dominique
authors.initials: D
authors.lastname: De Wit
authors.forename: Fabienne
authors.initials: F
authors.lastname: Willems
authors.forename: Pierre
authors.initials: P
authors.lastname: Van Damme
authors.forename: Michel
authors.initials: M
authors.lastname: Goldman
authors.forename: Stanislas
authors.initials: S
authors.lastname: Goriely
mesh_terms: D000328:Adult; D002478:Cells, Cultured; D002648:Child; D016207:Cytokines / Q000096:biosynthesis; D003713:Dendritic Cells; D005312:Fetal Blood / Q000166:cytology; D006803:Human Development; D006801:Humans; D007107:Immune System; D007223:Infant; D008070:Lipopolysaccharides / Q000494:pharmacology; D009000:Monocytes; D009838:Oligodeoxyribonucleotides / Q000494:pharmacology; D051197:Toll-Like Receptor 4 / Q000276:immunology*; D051217:Toll-Like Receptor 9 / Q000276:immunology*
chemical_list: C408982:CPG-oligonucleotide; D016207:Cytokines; D008070:Lipopolysaccharides; D009838:Oligodeoxyribonucleotides; C495345:TLR4 protein, human; C495371:TLR9 protein, human; D051197:Toll-Like Receptor 4; D051217:Toll-Like Receptor 9