...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>EBioMedicine >Circulating growth/differentiation factor 15 is associated with human CD56bright natural killer cell dysfunction and nosocomial infection in severe systemic inflammation
【24h】

Circulating growth/differentiation factor 15 is associated with human CD56bright natural killer cell dysfunction and nosocomial infection in severe systemic inflammation

机译：循环生长/分化因子15与人类CD56明亮的自然杀伤细胞功能障碍和严重系统性炎症中的医院感染有关

获取原文
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Background Systemic inflammation induced by sterile or infectious insults is associated with an enhanced susceptibility to life-threatening opportunistic, mostly bacterial, infections due to unknown pathogenesis. Natural killer (NK) cells contribute to the defence against bacterial infections through the release of Interferon (IFN) γ in response to Interleukin (IL) 12. Considering the relevance of NK cells in the immune defence we investigated whether the function of NK cells is disturbed in patients suffering from serious systemic inflammation. Methods NK cells from severely injured patients were analysed from the first day after the initial inflammatory insult until the day of discharge in terms of IL-12 receptor signalling and IFN-γ synthesis. Findings During systemic inflammation, the expression of the IL-12 receptor β2 chain, phosphorylation of signal transducer and activation 4, and IFN-γ production on/in NK cells was impaired upon exposure to Staphylococcus aureus . The profound suppression of NK cells developed within 24?h after the initial insult and persisted for several weeks. NK cells displayed signs of exhaustion. Extrinsic changes were mediated by the early and long-lasting presence of growth/differentiation factor (GDF) 15 in the circulation that signalled through the transforming growth factor β receptor I and activated Smad1/5. Moreover, the concentration of GDF-15 in the serum inversely correlated with the IL-12 receptor β2 expression on NK cells and was enhanced in patients who later acquired septic complications. Interpretation GDF-15 is associated with the development of NK cell dysfunction during systemic inflammation and might represent a novel target to prevent nosocomial infections. Fund The study was supported by the Department of Orthopaedics and Trauma Surgery, University Hospital Essen.
机译：背景技术由无菌或感染性感染引起的全身性炎症与由于未知发病机制而对威胁生命的机会性感染（主要是细菌性感染）的敏感性增加有关。天然杀伤（NK）细胞通过响应白细胞介素（IL）12释放干扰素（IFN）γ来增强抵抗细菌感染的能力。考虑到NK细胞在免疫防御中的相关性，我们研究了NK细胞的功能是否患有严重全身性炎症的患者不安。方法从IL-12受体信号转导和IFN-γ合成的角度，分析从严重炎症患者感染后的第一天到出院当天的严重损伤患者的NK细胞。研究结果在全身性炎症期间，暴露于金黄色葡萄球菌后，IL-12受体β2链的表达，信号转导的磷酸化和激活4以及NK细胞上/之中的IFN-γ产生均受到损害。 NK细胞的强烈抑制作用在最初的伤害后24小时内就出现了，并持续了数周。 NK细胞显示衰竭的迹象。外在变化是由循环中生长/分化因子（GDF）15的早期和持久存在介导的，该信号通过转化生长因子β受体I和活化的Smad1 / 5发出信号。此外，血清中GDF-15的浓度与NK细胞上IL-12受体β2的表达呈负相关，并且在后来感染脓毒症的患者中升高。解释GDF-15与全身性炎症期间NK细胞功能障碍的发展有关，可能代表预防医院感染的新靶标。基金该研究得到埃森大学医院骨科和创伤外科的支持。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号