In neonates S100A8/S100A9 alarmins prevent the expansion of a specific inflammatory monocyte population promoting septic shock
Heinemann AS, Pirr S, Fehlhaber B, Mellinger L, Burgmann J, Busse M, Ginzel M, Friesenhagen J, Von Koeckritz-Blickwede M, Ulas T, Von Kaisenberg CS, Roth J, Vogl T, Viemann D (2017)
Publication Type: Journal article
Publication year: 2017
Journal
Book Volume: 31
Pages Range: 1153-1164
Journal Issue: 3
Abstract
The high susceptibility of newborn infants to sepsis is ascribed to an immaturity 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 assigned to CD14+/human leukocyte antigen (HLA)-DR2/low/CD33+ monocytes in humans and to CD11b+/Gr-1int/Ly6G2/Ly6Chi cells in mice. We found monocytes with these phenotypes significantly expanded in their respective newborns. Functionally, however, they did not prove immunosuppressive but rather responded inflammatorily to microbial stimulation. Their expansion did not correlate with high S100A8/S100A9 levels in cord blood. Murine studies revealed an excessive expansion of CD11b+/Gr-1int/ Ly6G2/Ly6Chi monocytes in S100A9-/- neonates compared to wild-type neonates. This strong baseline expansion was associated with hyperinflammatory responses during endotoxemia and fatal septic courses. Treating S100A9-/- neonates directly after birth with S100A8/S100A9 alarmins prevented excessive expansion of this inflammatory monocyte population and death from septic shock. Our data suggest that a specific population of inflammatory monocytes promotesfatal coursesof sepsis inneonates if itsexpansionis not regulatedbyS100A8/S100A9alarmins.
Involved external institutions
Stiftung Tierärztliche Hochschule Hannover (TiHo)
Germany (DE)
Medizinische Hochschule Hannover (MHH) / Hannover Medical School
Germany (DE)
Rheinische Friedrich-Wilhelms-Universität Bonn
Germany (DE)
Westfälische Wilhelms-Universität (WWU) Münster
Germany (DE)
Germany (DE)
Medizinische Hochschule Hannover (MHH) / Hannover Medical School
Germany (DE)
Rheinische Friedrich-Wilhelms-Universität Bonn
Germany (DE)
Westfälische Wilhelms-Universität (WWU) Münster
Germany (DE)
How to cite
APA:
Heinemann, A.S., Pirr, S., Fehlhaber, B., Mellinger, L., Burgmann, J., Busse, M.,... Viemann, D. (2017). In neonates S100A8/S100A9 alarmins prevent the expansion of a specific inflammatory monocyte population promoting septic shock. The FASEB Journal, 31(3), 1153-1164. https://doi.org/10.1096/fj.201601083R
MLA:
Heinemann, Anna S., et al. "In neonates S100A8/S100A9 alarmins prevent the expansion of a specific inflammatory monocyte population promoting septic shock." The FASEB Journal 31.3 (2017): 1153-1164.
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