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, Schoening J, Schreek S, Pfeifer S, Reuner F, Voellger L, Stanulla M, Von Koeckritz-Blickwede M, Glander S, Barczyk-Kahlert K, Von Kaisenberg CS, Friesenhagen J, Fischer-Riepe L, Zenker S, Schultze JL, Roth J, Viemann D (2017)

Publication Type: Journal article

Publication year: 2017

Journal

Nature Immunology Nature Research

Book Volume: 18

Pages Range: 622-632

Journal Issue: 6

DOI: 10.1038/ni.3745

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.

Involved external institutions

Rheinische Friedrich-Wilhelms-Universität Bonn DE Germany (DE) Medizinische Hochschule Hannover (MHH) / Hannover Medical School DE Germany (DE) Stiftung Tierärztliche Hochschule Hannover (TiHo) DE Germany (DE) Westfälische Wilhelms-Universität (WWU) Münster DE Germany (DE)

How to cite

APA:

Ulas, T., Pirr, S., Fehlhaber, B., Bickes, M.S., Loof, T.G., Vogl, T.,... Viemann, D. (2017). S100-alarmin-induced innate immune programming protects newborn infants from sepsis. Nature Immunology, 18(6), 622-632. https://doi.org/10.1038/ni.3745

MLA:

Ulas, Thomas, et al. "S100-alarmin-induced innate immune programming protects newborn infants from sepsis." Nature Immunology 18.6 (2017): 622-632.

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