title: Responsiveness of human monocytes to the commensal bacterium Staphylococcus epidermidis develops late in gestation.
abstract: BACKGROUND
  Staphylococcus epidermidis (SE) rarely causes infection in term infants but is a leading cause of late-onset sepsis in preterm infants. We hypothesized that the innate immune responses to SE in preterm infants are impaired in a gestational age (GA)-dependent manner.
  
  
  METHODS
  Cord and peripheral blood mononuclear cells (MNCs) were stimulated with SE bacteria, and a range of innate immune responses were assessed, including phagocytosis, intracellular killing, Toll-like receptor (TLR) pathway transcriptional activation, cytokine production, TLR2 and TLR4 expression, and cell signaling.
  
  
  RESULTS
  Phagocytosis and intracellular killing of SE bacteria were similar in neonatal and adult monocytes. Cytokine gene expression and protein synthesis increased in a GA-dependent manner, which was confirmed at the single-cell level. These GA-related effects were not associated with differences in expression of TLR2 or TLR4, nor with downstream activation of nuclear factor-κB or mitogen-activated protein kinase pathways.
  
  
  CONCLUSIONS
  The expression of TLRs, phagocytic capacity, and intracellular killing by monocytes develops early in fetal development, whereas the ability to mount a bacteria-induced cytokine response requires further maturation. The functional immaturity of monocyte activation pathways in the preterm infant may underpin their particular susceptibility to sepsis with commensal bacteria.
authors.affiliation: University of Western Australia Centre for Neonatal Research and Education, Perth, Western Australia, Australia. tobias.strunk@health.wa.gov.au
authors.forename: Tobias
authors.initials: T
authors.lastname: Strunk
authors.forename: Amy
authors.initials: A
authors.lastname: Prosser
authors.forename: Ofer
authors.initials: O
authors.lastname: Levy
authors.forename: Victoria
authors.initials: V
authors.lastname: Philbin
authors.forename: Karen
authors.initials: K
authors.lastname: Simmer
authors.forename: Dorota
authors.initials: D
authors.lastname: Doherty
authors.forename: Adrian
authors.initials: A
authors.lastname: Charles
authors.forename: Peter
authors.initials: P
authors.lastname: Richmond
authors.forename: David
authors.initials: D
authors.lastname: Burgner
authors.forename: Andrew
authors.initials: A
authors.lastname: Currie
mesh_terms: D016207:Cytokines / Q000276:immunology; D005312:Fetal Blood / Q000166:cytology*; D005434:Flow Cytometry; D018507:Gene Expression Regulation, Developmental / Q000276:immunology*; D006801:Humans; D007113:Immunity, Innate / Q000276:immunology*; D009000:Monocytes / Q000276:immunology* / Q000378:metabolism; D010587:Phagocytosis / Q000276:immunology*; D015398:Signal Transduction / Q000276:immunology*; D013212:Staphylococcus epidermidis / Q000276:immunology*; D018709:Statistics, Nonparametric; D051193:Toll-Like Receptors / Q000276:immunology
chemical_list: D016207:Cytokines; D051193:Toll-Like Receptors