title: IL-15 and macrophage secretory factors facilitate immune activation of neonatal natural killer cells by lipoteichoic acid.
abstract: Neonates possess a relatively "naive", yet inducible immune system. Our hypothesis is that upon strategic antigen exposure, cytokine priming and sensitization by accessory cells, natural killer (NK) cells could be activated to become a functional phenotype. We investigated the in vitro stimulation of cord blood (CB) and adult NK cells upon challenge with lipoteichoic acid (LTA), interleukin (IL)-15 and LTA-primed autologous macrophage-conditioned medium, using CD107a and CD69 phenotypes as indicators of activation. We also examined response of CB macrophages to LTA, in terms of P44/42 extracellular signal-regulated kinases (ERK1/2) activation and cytokine secretion. LTA significantly induced secretion of inflammatory cytokines tumor necrotic factor (TNF)-α, IL-6, IL-12 and activated the upstream signal of ERK1/2 phosphorylation in neonatal macrophages. The magnitude of responses to stimulation differed between neonatal and adult NK cells. Co-stimulation with IL-15 was critical for expansion of the CD69 and CD107a NK subpopulations in both neonatal and adult cells, upon a LTA challenge. NK cell activation could be enhanced by LTA-primed autologous macrophages through secretory factors. Our results indicated that neonatal macrophages and NK cells can evoke immunologic responses to a Gram-positive bacterial antigen. The combinatory priming strategy is relevant for development of novel protocols, such as IL-15 treatment, to compensate for the immaturity of the innate immune system in newborns against bacterial infections.
authors.affiliation: Department of Paediatrics, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, NT, Hong Kong.
authors.forename: Siu Fung
authors.initials: SF
authors.lastname: Cheng
authors.forename: Joanna Wen Ying
authors.initials: JW
authors.lastname: Ho
authors.forename: Kathy Yuen Yee
authors.initials: KY
authors.lastname: Chan
authors.forename: Tak Yeung
authors.initials: TY
authors.lastname: Leung
authors.forename: Hugh Simon
authors.initials: HS
authors.lastname: Lam
authors.forename: Oi Ning
authors.initials: ON
authors.lastname: Fong
authors.forename: Karen
authors.initials: K
authors.lastname: Li
authors.forename: Pak Cheung
authors.initials: PC
authors.lastname: Ng
mesh_terms: D000328:Adult; D015703:Antigens, CD / Q000378:metabolism; D000945:Antigens, Differentiation, T-Lymphocyte / Q000378:metabolism; D017077:Culture Media, Conditioned / Q000494:pharmacology; D016207:Cytokines / Q000378:metabolism; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005312:Fetal Blood / Q000166:cytology; D006801:Humans; D007231:Infant, Newborn; D019409:Interleukin-15 / Q000276:immunology*; D007694:Killer Cells, Natural / Q000187:drug effects / Q000276:immunology*; D037181:Lectins, C-Type / Q000378:metabolism; D008070:Lipopolysaccharides / Q000276:immunology* / Q000494:pharmacology; D052118:Lysosomal-Associated Membrane Protein 1 / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects / Q000201:enzymology / Q000276:immunology* / Q000378:metabolism*; D008297:Male; D010766:Phosphorylation / Q000187:drug effects; D013682:Teichoic Acids / Q000276:immunology* / Q000494:pharmacology; D055815:Young Adult; D000099192:CD69 Antigens
chemical_list: D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D017077:Culture Media, Conditioned; D016207:Cytokines; D048049:Extracellular Signal-Regulated MAP Kinases; D019409:Interleukin-15; D037181:Lectins, C-Type; D008070:Lipopolysaccharides; D052118:Lysosomal-Associated Membrane Protein 1; D013682:Teichoic Acids; D000099192:CD69 Antigens; C009900:lipoteichoic acid