Granulocytic Myeloid-Derived Suppressor Cells (GR-MDSC) in Breast Milk (BM); GR-MDSC Accumulate in Human BM and
Natascha Köstlin1, Carolin Schoetensack1, Julian Schwarz1
1Department of Neonatology, Tuebingen University Children's Hospital, Tuebingen, Germany.
Insights
Myeloid-derived suppressor cells (MDSC) in breast milk (BM) show immune-modulatory properties. These cells may protect infants from serious gut infections like necrotizing enterocolitis (NEC) and nosocomial bacterial infections (NBI).
Area of Science:
- Immunology
- Neonatal Research
- Microbiology
Background:
- Nosocomial bacterial infections (NBI) and necrotizing enterocolitis (NEC) are leading causes of mortality in preterm infants.
- Breast milk (BM) feeding is protective, but the underlying mechanisms remain unclear.
- Myeloid-derived suppressor cells (MDSC) are known for immune regulation in pregnancy and newborns.
Purpose of the Study:
- To investigate the presence and function of MDSC in human breast milk.
- To determine if MDSC in breast milk contribute to the protective effects of breastfeeding.
Main Methods:
- Analysis of MDSC in breast milk and maternal peripheral blood.
- Assessment of MDSC phenotype, suppressive activity, and modulation of TLR-expression on monocytes.
- Investigation of the role of lactotrophic hormones (prolactin, oxytocin) on MDSC induction.
Main Results:
- Granulocytic MDSC, not monocytic MDSC, were found to accumulate in breast milk.
- Breast milk MDSC exhibited an activated phenotype and increased suppressive activity.
- Prolactin and oxytocin did not induce MDSC from peripheral blood.
Conclusions:
- This study identifies immune-modulatory MDSC in human breast milk for the first time.
- MDSC in breast milk may play a crucial role in local gut immune modulation.
- These findings suggest a potential protective mechanism against NBI and NEC in infants.
Abstract:
Nosocomial bacterial infections (NBI) and necrotizing enterocolitis (NEC) are among the main reasons for death in preterm infants. Both are often caused by bacteria coming from the infected infant's gut and feeding with breast milk (BM) seems beneficial in their pathogenesis. However, mechanisms causing the protective effect of BM are only incompletely understood. Myeloid-derived suppressor cells (MDSC) are myeloid cells with suppressive activity on other immune cells, recently described to play a role in mediating maternal-fetal tolerance during pregnancy and immune adaptation in newborns. Until now, nothing is known about occurrence and function of MDSC in BM. We analyzed MDSC in BM and peripheral blood of breastfeeding mothers and found that granulocytic MDSC, but not monocytic MDSC, accumulate in BM, exhibit an activated phenotype and increased suppressive activity and modulate TLR-expression on monocytes. Furthermore, we found that the lactotrophic hormones prolactin and oxytocin do not induce MDSC from peripheral blood. This is the first study to describe MDSC with immune-modulatory properties in human BM. Our results point toward a role for MDSC in local immune modulation in the gut possibly protecting infants from NBI and NEC.
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