期刊
PEDIATRIC RESEARCH
卷 86, 期 5, 页码 608-615出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/s41390-019-0504-7
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- Medical Faculty of Tuebingen University [E.05.00433]
- Federal Ministry of Education and Research (BMBF)
- Ministry for Science, Research and Art of Baden-Wurttemberg (MWKBW)
- European Social Fund (ESF)
- German Centre for Infection Research (DZIF)
BACKGROUND: Neonatal sepsis is a leading cause of perinatal morbidity and mortality. In comparison to adults, neonates exhibit a higher susceptibility to infections. Myeloid-derived suppressor cells (MDSCs) are myeloid cells with suppressive activity on other immune cells accumulating during foetal life and controlling inflammation in neonates. Most studies investigating the mechanisms for MDSC-mediated immune suppression have been focused on T-cells. Thus far, little is known about the role of MDSC for monocyte function. METHODS: The impact of human cord blood MDSCs (CB-MDSCs) on monocytes was investigated in an in vitro model. CB-MDSCs were co-cultured with peripheral blood mononuclear cells and monocytes were analysed for expression of surface markers, T cell stimulatory and phagocytic capacity, as well as the production of intracellular cytokines by flow cytometry. RESULTS: CB-MDSCs increased the expression of co-inhibitory molecules and decreased the expression of major histocompatibility complex class II molecules on monocytes, leading to an impaired T-cell stimulatory capacity. Upon bacterial stimulation, expression of phagocytosis receptors, phagocytosis rates and production of tumor necrosis factor-a by monocytes was diminished by CB-MDSCs. CONCLUSION: We show that CB-MDSCs profoundly modulate monocyte functions, thereby indirectly impairing T-cell activation. Further research is needed to figure out if MDSCs could be a therapeutic target for inflammatory diseases in neonates like neonatal sepsis.
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