title: Hierarchical maturation of innate immune defences in very preterm neonates.
abstract: BACKGROUND
  Preterm neonates are highly vulnerable to infection.
  
  
  OBJECTIVE
  To investigate the developmental contribution of prematurity, chorioamnionitis and antenatal corticosteroids (ANS) on the maturation of neonatal microbial pathogen recognition responses.
  
  
  METHODS
  Using standardized protocols, we assayed multiple inflammatory cytokine responses (IL-1β, IL-6, TNF-α and IL-12/23p40) to three prototypic Toll-like receptor (TLR) agonists, i.e. TLR4 (lipopolysaccharide), TLR5 (flagellin) and TLR7/8 (R848), and to the non-TLR retinoic acid-inducible gene I (RIG-I)-like receptor agonist, in cord blood mononuclear cells from neonates born before 33 weeks of gestation and at term.
  
  
  RESULTS
  TLR responses develop asynchronously in preterm neonates, whereby responses to TLR7/8 were more mature and were followed by the development of TLR4 responses, which were also heterogeneous. Responses to TLR5 were weakest and most immature. Maturity in TLR responses was not influenced by sex. Overall, we detected no significant contribution of ANS and chorioamnionitis to the developmental attenuation of either TLR or RIG-I responses.
  
  
  CONCLUSIONS
  The maturation of anti-microbial responses in neonates born early in gestation follows an asynchronous developmental hierarchy independently of an exposure to chorioamnionitis and ANS. Our data provide an immunological basis for the predominance of specific microbial infections in this age group.
authors.affiliation: Child and Family Research Institute, Vancouver, B.C., Canada.
authors.forename: Ashish Arunkumar
authors.initials: AA
authors.lastname: Sharma
authors.forename: Roger
authors.initials: R
authors.lastname: Jen
authors.forename: Rollin
authors.initials: R
authors.lastname: Brant
authors.forename: Mihoko
authors.initials: M
authors.lastname: Ladd
authors.forename: Qing
authors.initials: Q
authors.lastname: Huang
authors.forename: Amanda
authors.initials: A
authors.lastname: Skoll
authors.forename: Christof
authors.initials: C
authors.lastname: Senger
authors.forename: Stuart E
authors.initials: SE
authors.lastname: Turvey
authors.forename: Nico
authors.initials: N
authors.lastname: Marr
authors.forename: Pascal M
authors.initials: PM
authors.lastname: Lavoie
mesh_terms: D000305:Adrenal Cortex Hormones / Q000008:administration & dosage / Q000276:immunology; D019540:Area Under Curve; D002821:Chorioamnionitis / Q000276:immunology; D005260:Female; D005312:Fetal Blood / Q000276:immunology; D005408:Flagellin / Q000276:immunology; D006801:Humans; D007093:Imidazoles / Q000276:immunology; D007113:Immunity, Innate / Q000276:immunology*; D062071:Infant, Extremely Premature / Q000276:immunology*; D007231:Infant, Newborn; D053762:Interleukin-12 Subunit p40 / Q000097:blood; D053583:Interleukin-1beta / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D016014:Linear Models; D008070:Lipopolysaccharides / Q000276:immunology; D008297:Male; D011247:Pregnancy; D051193:Toll-Like Receptors / Q000819:agonists / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
chemical_list: D000305:Adrenal Cortex Hormones; D007093:Imidazoles; D053762:Interleukin-12 Subunit p40; D053583:Interleukin-1beta; D015850:Interleukin-6; D008070:Lipopolysaccharides; D051193:Toll-Like Receptors; D014409:Tumor Necrosis Factor-alpha; D005408:Flagellin; C402365:resiquimod