IL-15 and macrophage secretory factors facilitate immune activation of neonatal natural killer cells by lipoteichoic acid
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AbstractNeonates 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)-alpha, 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. (c) 2012 Elsevier Ltd. All rights reserved.
All Author(s) ListCheng SF, Ho JWY, Chan KYY, Leung TY, Lam HS, Fong ON, Li KR, Ng PC
Journal nameCytokine
Volume Number61
Issue Number2
Pages499 - 505
LanguagesEnglish-United Kingdom
KeywordsIL-15; Lipoteichoic acid; Macrophages; Natural killer cells; Neonatal blood
Web of Science Subject CategoriesBiochemistry & Molecular Biology; BIOCHEMISTRY & MOLECULAR BIOLOGY; Cell Biology; CELL BIOLOGY; Immunology; IMMUNOLOGY

Last updated on 2021-11-10 at 00:09