Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2017 Jun;18(6):622-632.
doi: 10.1038/ni.3745. Epub 2017 May 1.

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

Thomas Ulas  1 , Sabine Pirr  2 , Beate Fehlhaber  2 , Marie S Bickes  2 , Torsten G Loof  3 , Thomas Vogl  4 , Lara Mellinger  2 , Anna S Heinemann  2 , Johanna Burgmann  2 , Jennifer Schöning  2 , Sabine Schreek  2 , Sandra Pfeifer  3 , Friederike Reuner  3 , Lena Völlger  2 , Martin Stanulla  5 , Maren von Köckritz-Blickwede  3 , Shirin Glander  6 , Katarzyna Barczyk-Kahlert  4 , Constantin S von Kaisenberg  7 , Judith Friesenhagen  2 , Lena Fischer-Riepe  4 , Stefanie Zenker  4 , Joachim L Schultze  1   8 , Johannes Roth  4 , Dorothee Viemann  2
Affiliations

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

Thomas Ulas et al. Nat Immunol. 2017 Jun.

Erratum in

  • Corrigendum: S100-alarmin-induced innate immune programming protects newborn infants from sepsis.
    Ulas T, Pirr S, Fehlhaber B, Bickes MS, Loof TG, Vogl T, Mellinger L, Heinemann AS, Burgmann J, Schöning J, Schreek S, Pfeifer S, Reuner F, Völlger L, Stanulla M, von Köckritz-Blickwede M, Glander S, Barczyk-Kahlert K, von Kaisenberg CS, Friesenhagen J, Fischer-Riepe L, Zenker S, Schultze JL, Roth J, Viemann D. Ulas T, et al. Nat Immunol. 2017 Sep 19;18(10):1173. doi: 10.1038/ni1017-1173b. Nat Immunol. 2017. PMID: 28926540 No abstract available.

Abstract

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 impairing pathogen defense. TRIF-adaptor-dependent regulatory genes remained unaffected by perinatal S100 programming and responded strongly to lipopolysaccharide, but were barely expressed. Steady-state expression of TRIF-dependent genes increased only gradually during the first year of life in human neonates, shifting immune regulation toward the adult phenotype. Disruption of this critical sequence of transient alarmin programming and subsequent reprogramming of regulatory pathways increased the risk of hyperinflammation and sepsis. Collectively these data suggest that neonates are characterized by a selective, transient microbial unresponsiveness that prevents harmful hyperinflammation in the delicate neonate while allowing for sufficient immunological protection.

PubMed Disclaimer

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Nat Rev Immunol. 2015 Jan;15(1):7-17 - PubMed
    1. PLoS Pathog. 2012;8(10):e1002987 - PubMed
    1. Source Code Biol Med. 2011 Apr 07;6:7 - PubMed
    1. Mol Med. 2015 Jun 02;21:496-504 - PubMed
    1. PLoS One. 2010 Nov 15;5(11):e13984 - PubMed

Publication types

MeSH terms

LinkOut - more resources