Department of Neonatology, Tuebingen University Children's Hospital, Tuebingen, Germany.
Private Practice in Gynecology and Obstetrics, Tuebingen, Germany.
Front Immunol. 2018 May 17;9:1098. doi: 10.3389/fimmu.2018.01098. eCollection 2018.
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.
医院获得性细菌感染（NBI）和坏死性小肠结肠炎（NEC）是早产儿死亡的主要原因之一。这两种疾病通常都是由感染婴儿肠道中的细菌引起的，而母乳喂养（BM）似乎对其发病机制有益。然而，导致 BM 保护作用的机制尚不完全清楚。髓源性抑制细胞（MDSC）是具有抑制其他免疫细胞活性的髓系细胞，最近研究表明其在怀孕期间介导母婴耐受和新生儿免疫适应中发挥作用。到目前为止，关于 MDSC 在 BM 中的发生和功能还一无所知。我们分析了哺乳期母亲的 BM 和外周血中的 MDSC，发现粒细胞 MDSC 而非单核细胞 MDSC 在 BM 中积累，表现出激活表型和增强的抑制活性，并调节单核细胞上的 TLR 表达。此外，我们发现催乳激素催乳素和催产素不会从外周血诱导 MDSC。这是首次在人类 BM 中描述具有免疫调节特性的 MDSC 的研究。我们的研究结果表明 MDSC 可能在肠道的局部免疫调节中发挥作用，从而保护婴儿免受 NBI 和 NEC 的侵害。
