In neonates S100A8/S100A9 alarmins prevent the expansion of a specific inflammatory monocyte population promoting septic shock

@article{Heinemann2017InNS,
  title={In neonates S100A8/S100A9 alarmins prevent the expansion of a specific inflammatory monocyte population promoting septic shock},
  author={Anna S. Heinemann and Sabine Pirr and Beate Fehlhaber and Lara Mellinger and Johanna Burgmann and Mandy Busse and Marco Ginzel and Judith Friesenhagen and Maren von K{\"o}ckritz-Blickwede and Thomas Ulas and Constantin S. Kaisenberg and Johannes Roth and Thomas Vogl and Dorothee Viemann},
  journal={The FASEB Journal},
  year={2017},
  volume={31},
  pages={1153 - 1164}
}
The high susceptibility of newborn infants to sepsis is as cribed to animmaturity of the neonatal immune system, but the molecular mechanisms remain unclear. Newborn monocytes massively release the alarmins S100A8/S100A9. In adults, these are major regulators of immunosuppressive myeloid‐derived suppressor cells (MDSCs). We investigated whether S100A8/S100A9 cause an expansion of monocytic MDSCs (Mo‐MDSCs) in neonates, thereby contributing to an immunocompromised state. Mo‐MDSCs have been… 
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S100A8/A9 is the first predictive marker for neonatal sepsis
TLDR
Serum S100A8/A9 proved as an independent predictive marker of late-onset neonatal sepsis (LOS) in preterm infants, which for the first time offers the opportunity to change current treatment policies by improving antibiotic stewardship and timely individualized therapeutic intervention.
Neutrophil extracellular traps (NETs) exacerbate severity of infant sepsis
TLDR
This study reveals a hitherto unrecognized mechanism of pediatric sepsis susceptibility and suggests that NETs represents a potential target to improve clinical outcomes of sepsi.
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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