Abstract
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-α 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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Acknowledgements
This work has been supported by the research funds from the Medical Faculty of Tuebingen University (grant no. E.05.00433), the Federal Ministry of Education and Research (BMBF), the Ministry for Science, Research and Art of Baden-Württemberg (MWKBW), the European Social Fund (ESF) and the German Centre for Infection Research (DZIF).
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N.K.-G. and C.G. conceptualized and designed the study. N.K.-G., S.D., J.S., M.V., K.M. and B.S. performed experiments. N.K.-G., S.D., M.V. and C.G. analysed data. N.K.-G. drafted the initial manuscript. N.K.-G., T.W.O., C.F.P., F.W., U.H. and C.G. reviewed and revised the manuscript. All authors approved the final manuscript as submitted and agreed to be accountable for all aspects of the work.
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Dietz, S., Schwarz, J., Vogelmann, M. et al. Cord blood granulocytic myeloid-derived suppressor cells impair monocyte T cell stimulatory capacity and response to bacterial stimulation. Pediatr Res 86, 608–615 (2019). https://doi.org/10.1038/s41390-019-0504-7
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DOI: https://doi.org/10.1038/s41390-019-0504-7
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