Depletion of neonatal neutrophilic cells worsens the outcome of E. coli sepsis in newborn mice

Neonates are particularly susceptible to infections because of a reduced ability to fight bacterial pathogens while simultaneously exhibiting enhanced inflammatory damage. Neonatal neutrophilic cells (NNC) are a heterogeneous population of innate immune cells, which differ substantially from adults....

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Main Authors: Schwarz, Julian (Author) , Hebel, Janine (Author) , Dietz-Ziegler, Stefanie (Author) , Rühle, Jessica (Author) , Lajqi, Trim (Author) , Orlikowsky, Thorsten (Author) , Poets, Christian F. (Author) , Gille, Christian (Author) , Köstlin-Gille, Natascha (Author)
Format: Article (Journal)
Language:English
Published: April 2026
In: European journal of immunology
Year: 2026, Volume: 56, Issue: 4, Pages: 1-15
ISSN:1521-4141
DOI:10.1002/eji.70171
Online Access:Verlag, kostenfrei, Volltext: https://doi.org/10.1002/eji.70171
Verlag, kostenfrei, Volltext: https://onlinelibrary.wiley.com/doi/abs/10.1002/eji.70171
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Author Notes:Julian Schwarz, Janine Hebel, Stefanie Dietz-Ziegler, Jessica Rühle, Trim Lajqi, Thorsten Orlikowsky, Christian F. Poets, Christian Gille, Natascha Köstlin-Gille
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Summary:Neonates are particularly susceptible to infections because of a reduced ability to fight bacterial pathogens while simultaneously exhibiting enhanced inflammatory damage. Neonatal neutrophilic cells (NNC) are a heterogeneous population of innate immune cells, which differ substantially from adults. They display functional deficits in pro-inflammatory responses and include a suppressive subpopulation known as myeloid-derived suppressor cells (MDSC). It remains unclear whether pro- or anti-inflammatory properties of NNC predominate immediately after birth. This study aimed to clarify the role of neutrophilic cells in neonatal murine sepsis. We established a neonatal mouse model of E. coli-sepsis and depleted NNC using an anti-Ly6G antibody to assess mortality, bacterial load, cytokine responses, and immune cell composition. A dose of 30,000 CFU E. coli resulted in a 67% survival rate in neonatal mice with litters of 5-6 pups, while mortality increased in larger litters. NNC-depletion significantly increased mortality and systemic inflammation during neonatal sepsis, whereas bacterial load was only minimally affected. Other immune cell populations remained unchanged. E. coli sepsis induced pronounced neutrophil infiltration into organs of adults, whereas neonates exhibit reduced numbers of NNC in affected organs. Overall, our findings suggest that NNC-mediated control of inflammation may protect neonates from lethal sepsis.
Item Description:Online veröffentlicht: 29. März 2026
Gesehen am 09.06.2026
Physical Description:Online Resource
ISSN:1521-4141
DOI:10.1002/eji.70171