Publication in Nature Immunology: Babies are born with a throttled immune system

This is shown by a study conducted by the Medical University of Hannover and the Universities of Bonn and Münster.

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from left: Dr. Thomas Ulas and Prof. Dr. Joachim L. Schultze (c) Foto: Volker Lannert/Uni Bonn

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, it could be 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.

Publication:

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. S100-alarmin-induced innate immune programming protects newborn infants from sepsis. Nat Immunol. 2017 May 1. doi: 10.1038/ni.3745. [Epub ahead of print] PMID: 28459433

Prof. Dr. Joachim Schultze & Dr. Thomas Ulas 
LIMES-Institut, Genomik & Immunregulation 
Universität Bonn 
Tel.: 0228/73-6 27 87 

j.schultze@uni-bonn.de, thomas.ulas@uni-bonn.de