Myeloid-derived suppressor cells control microbial sepsis
Myeloid-derived suppressor cells control microbial sepsis
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DOI：
10.1007/s00134-012-2574-4
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发表时间：
2012-06-01
影响因子：
38.9
通讯作者：
Gibot, Sebastien
中科院分区：
文献类型：
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作者：
Derive, Marc;Bouazza, Youcef;Gibot, Sebastien
探讨骨髓源性抑制细胞（MDSC）在脓毒症小鼠中的作用。MDSC是在癌症、炎症和感染期间扩增的异质细胞群。这些细胞通过其抑制T淋巴细胞增殖的能力，调节各种疾病期间的免疫应答。在微生物感染过程中，它们的作用几乎不为人所知。在成年雄性BALB/c小鼠中，通过盲肠结扎和穿孔诱导脓毒性休克;假手术动物作为对照。在麻醉状态下处死动物以收获血液和器官。多微生物脓毒症诱导MDSC在存活小鼠的脾脏中进行性积累，发现脾脏在存活小鼠中增大。在感染开始后第10天收获的MDSC在细胞因子分泌、NF-kB活化、ROS产生和LPS酶I活性方面对LPS高度响应，而早期出现（第3天）的MDSC对该刺激的响应较差。相比之下，第3天和第10天的MDSC都能够抑制T细胞增殖。连续转移10天的MDSCs到脓毒症小鼠，减少腹膜细胞因子的产生，增加细菌清除率，显着提高存活率。这些结果提供了新的信息MDSCs的作用，表明在脓毒症的保护作用。因此，应进一步研究已知可促进MDSC扩增的药物用于脓毒症治疗。
To investigate the role of myeloid-derived suppressor cells (MDSCs) during sepsis in mice. MDSCs are a heterogeneous population of cells that expand during cancer, inflammation and infection. These cells, by their ability to suppress T lymphocyte proliferation, regulate immune responses during various diseases. Their role during microbial infections is scarcely known.Septic shock was induced by caecal ligation and puncture in adult male BALB/c mice; sham-operated animals served as controls. Animals were killed under anaesthesia to harvest blood and organs.Polymicrobial sepsis induced a progressive accumulation of MDSCs in spleens that were found to be enlarged in surviving mice. MDSCs harvested at day 10 after the onset of infection were highly responsive to LPS in terms of cytokines secretion, NF-kB activation, ROS production and arginase I activity, whereas early-appearing (day 3) MDSCs poorly responded to this stimulus. By contrast, both day 3 and day 10 MDSCs were able to inhibit T cell proliferation. Adoptive transfer of day 10 MDSCs to septic mice attenuated peritoneal cytokine production, increased bacterial clearance and dramatically improved survival rate.These results provide new information on the role of MDSCs, suggesting a protective effect during sepsis. Pharmacologic agents known to promote the expansion of MDSCs should thus be further studied for sepsis treatment.