Neonatal myeloid derived suppressor cells show reduced apoptosis and immunosuppressive activity upon infection with Escherichia coli
Neonatal myeloid derived suppressor cells show reduced apoptosis and immunosuppressive activity upon infection with Escherichia coli
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DOI：
10.1002/eji.201646621
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发表时间：
2017-06-01
影响因子：
5.4
通讯作者：
Gille, Christian
中科院分区：
文献类型：
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作者：
Leiber, Anja;Schwarz, Julian;Gille, Christian
新生儿时期对感染的易感性和新生儿炎症控制能力的下降归因于胎儿期持续存在的免疫抑制。骨髓源性抑制细胞（MDSC）是未成熟的骨髓祖细胞，具有抑制活性，并且在脐带血中数量增加。我们假设 MDSC 有助于新生儿的先天宿主防御，同时也有抗炎信号传导。新生儿粒细胞 MDSC (G-MDSC) 的吞噬活性、感染诱导的细胞凋亡、B 细胞淋巴瘤 (Bcl)-2 家族蛋白的表达、活性氧 (ROS) 的产生、细胞因子的产生和 T 细胞抑制 将大肠杆菌（E. coli）感染与新生儿自体成熟多形核白细胞（PMN）进行比较。大肠杆菌感染后G-MDSCs的吞噬活性与成熟PMN相同，但G-MDSCs的凋亡减少。与 PMN 相比，G-MDSC 显示出增强的 Bcl-2 表达和较低的 ROS 产生。抑制 Bcl-2 可使 G-MDSC 的凋亡率降低至成熟 PMN 的凋亡率。与 PMN 相比，G-MDSC 中抗炎转化生长因子 β (TGF-β) 的诱导增强，而促炎性 IL-8 减少。受感染的 G-MDSC 强烈抑制 T 细胞的增殖。我们展示了 G-MDSC 在抗菌宿主防御中的直接作用。延长的存活时间和抗炎能力表明 G-MDSC 对于细菌感染后的免疫调节很重要。
Susceptibility to infection during the neonatal period and reduced control of inflammation in neonates are attributed to immunosuppression persisting from fetal life. Myeloid-derived suppressor cells (MDSCs) are immature myeloid progenitors with suppressive activity and increased numbers in cord blood. We hypothesized that MDSCs contribute to innate host defence in neonates, paralleled by anti-inflammatory signalling.Phagocytic activity, infection induced apoptosis, expression of B-cell lymphoma (Bcl)-2 family proteins, production of reactive oxygen species (ROS), cytokine production and T-cell suppression of neonatal granulocytic-MDSCs (G-MDSCs) after infection with Escherichia coli (E. coli) were compared to neonatal autologous mature polymorphonuclear leukocytes (PMNs). Phagocytic activity of G-MDSCs upon infection with E. coli was equal to that of mature PMNs, however, apoptosis of G-MDSCs was decreased. G-MDSCs showed enhanced Bcl-2-expression and lower ROS production compared to PMNs. Inhibition of Bcl-2 reduced apoptosis rates of G-MDSCs to that of mature PMNs. Induction of anti-inflammatory transforming growth factor beta (TGF-beta) was enhanced, while pro-inflammatory IL-8 decreased in G-MDSCs compared to PMNs. Infected G-MDSCs strongly suppressed proliferation of T cells. We show a direct role of G-MDSCs for anti-bacterial host defence. Prolonged survival and anti-inflammatory capacity suggest that G-MDSCs are important for immune-regulation after bacterial infection.