Cord Blood Monocytes, Neutrophils and Lymphocytes from Preterm and Full-Term Neonates Show Multiple Aberrations in Signalling Profiles Measured Using Phospho-Specific Whole-Blood Flow Cytometry

Authors

  • I. Nupponen,

    1. Department of Bacteriology and Immunology, Haartman Institute, University of Helsinki, Helsinki, Finland
    2. Department of Neonatology, Hospital for Children and Adolescents, Helsinki University Central Hospital, Helsinki, Finland
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  • A. Kuuliala,

    Corresponding author
    1. Department of Bacteriology and Immunology, Haartman Institute, University of Helsinki, Helsinki, Finland
    • Correspondence to: A. Kuuliala, Department of Bacteriology and Immunology, Haartman Institute, University of Helsinki, Haartmaninkatu 3, FIN-00014 Helsingin Yliopisto, Finland. E-mail: antti.kuuliala@gmail.com

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  • S. Siitonen,

    1. Laboratory Services (HUSLAB), Helsinki University Central Hospital, Helsinki, Finland
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  • H. Repo,

    1. Department of Bacteriology and Immunology, Haartman Institute, University of Helsinki, Helsinki, Finland
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  • K. Kuuliala

    1. Department of Bacteriology and Immunology, Haartman Institute, University of Helsinki, Helsinki, Finland
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Abstract

Immaturity of the immune system renders newborns susceptible to infections. We searched for aberrations in leucocyte signalling profiles, using phospho-specific whole-blood flow cytometry, in cord blood of nine preterm (two born before 32nd gestational week) and nine full-term infants, born by caesarean section. Thirteen adults served as reference subjects. Monocyte NF-κB phosphorylation following tumour necrosis factor (TNF) or bacterial stimulation was higher in preterm neonates than in full-term neonates or adults, p38 phosphorylation following bacterial stimulation was higher in both preterm and full-term neonates than in adults, while STAT1 phosphorylation by IFN-γ or IL-6, STAT3 phosphorylation by IL-6 and STAT5 phosphorylation by GM-CSF were lower in both full-term and preterm neonates than in adults. Neutrophil STAT1 and STAT3 phosphorylation following IFN-γ stimulation and STAT5 phosphorylation following GM-CSF stimulation were lower in newborn neonates than in adults. In both CD3+CD4+ and CD3+CD8+ lymphocytes, NF-κB phosphorylation by TNF was higher and STAT5 phosphorylation by IL-2 was lower in preterm and full-term newborns than in adults. STAT6 phosphorylation by IL-4 was comparable in monocytes and lymphocytes of newborns and adults. The results suggest that innate immune signalling pathways responding to inflammatory stimuli are strongly functional in leucocytes of preterm neonates, which may render these neonates susceptible to inappropriate tissue injury. In leucocytes of both preterm and full-term newborns, responses needed against intracellular pathogens, and regulatory functions show immaturities, possibly contributing to worse control of infections.

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