S100-alarmin-induced innate immune programming protects newborn infants from sepsis

@article{Ulas2017S100alarmininducedII,
  title={S100-alarmin-induced innate immune programming protects newborn infants from sepsis},
  author={Thomas Ulas and Sabine Pirr and Beate Fehlhaber and Marie S Bickes and Torsten G. Loof and Thomas Vogl and Lara Mellinger and Anna S. Heinemann and Johanna Burgmann and Jennifer Schöning and Sabine Schreek and Sandra Pfeifer and Friederike Reuner and Lena V{\"o}llger and Martin Stanulla and Maren von K{\"o}ckritz-Blickwede and Shirin Glander and Katarzyna Barczyk-Kahlert and Constantin von Kaisenberg and Judith Friesenhagen and Lena Fischer-Riepe and Stefanie Zenker and Joachim L. Schultze and Johannes Roth and Dorothee Viemann},
  journal={Nature Immunology},
  year={2017},
  volume={18},
  pages={622-632}
}
The high risk of neonatal death from sepsis is thought to result from impaired responses by innate immune cells; however, the clinical observation of hyperinflammatory courses of neonatal sepsis contradicts this concept. Using transcriptomic, epigenetic and immunological approaches, we demonstrated that high amounts of the perinatal alarmins S100A8 and S100A9 specifically altered MyD88-dependent proinflammatory gene programs. S100 programming prevented hyperinflammatory responses without… 
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Constitutive TNF‐α signaling in neonates is essential for the development of tissue‐resident leukocyte profiles at barrier sites
  • Marie S Bickes, S. Pirr, D. Viemann
  • Biology, Medicine
    FASEB journal : official publication of the Federation of American Societies for Experimental Biology
  • 2019
TLDR
It is demonstrated that healthy neonates showed already strong endothelial baseline activation, which was mediated by a constitutively increased production of TNF‐α, which suggests that constitutive TNF—mediated sterile endothelial activation in newborn infants contributes to the increased risk of developing SIRS but is needed to ensure the postnatal recruitment of leukocytes to organs and interfaces.
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The enteral supply of bioavailable, antimicrobially active amounts of S100-alarmins might be a promising option to protect newborns at high risk from infections and sepsis.
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TLDR
The presence of MDSCs and their functional activity in infants are closely associated with the maturity of newborns and the presence of lactoferrin (LF) in serum, suggesting that cell therapy with LF-MDSCs may provide potent therapeutic benefits in infants with various pathological conditions associated with dysregulated inflammation.
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