Fighting infant infections with myeloid-derived suppressor cells
Rebekka Weber, Viktor Umansky
Rebekka Weber, Viktor Umansky
Published September 4, 2019
Citation Information: J Clin Invest. 2019;129(10):4080-4082. https://doi.org/10.1172/JCI131649.
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Fighting infant infections with myeloid-derived suppressor cells

Abstract

Recent work demonstrated a role for myeloid-derived suppressor cells (MDSCs) in the antimicrobial response in newborns, but the signals guiding their differentiation remained unknown. In this issue of the JCI, Liu et al. demonstrate that lactoferrin (LF) converts newborn neutrophils and monocytes to MDSCs via the low-density lipoprotein receptor–related protein-2 (LRP2) receptor and NF-κB activation. Due to their strong antimicrobial activity, adoptive transfer of MDSCs generated by in vitro culture with LF prolonged the survival of newborn mice with necrotizing enterocolitis, a severe pathology in preterm infants. These findings indicate a surprising protective role of MDSCs in newborns and demonstrate the potential of MDSC therapy for the treatment of infants with diseases associated with deregulated inflammation.

Authors

Rebekka Weber, Viktor Umansky

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Figure 1

MDSCs protect newborns from inflammatory disorders.

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MDSCs protect newborns from inflammatory disorders. Preterm neonates sho...
Preterm neonates show a lower abundance of PMN-MDSCs and LF as compared with full-term neonates. The amount of PMN-MDSCs and LF is further decreased in preterm neonates with NEC as compared with those without this disease. PMN-MDSCs in healthy newborns produce NO, PGE2, and S100A9, suppressing T cell activities and exerting simultaneously antibacterial properties. MDSCs could be generated in vitro from newborn (but not adult) monocytes and neutrophils via the binding of LF to its receptor LRP2 on these cells. Mice with different pathological inflammatory conditions were successfully treated with in vitro–generated MDSCs, suggesting that such cell therapy could be efficient in newborns with NEC and other inflammatory disorders.