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首页> 外文期刊>Journal of Leukocyte Biology: An Official Publication of the Reticuloendothelial Society >Eosinophils induce DC maturation, regulating immunity.
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Eosinophils induce DC maturation, regulating immunity.

机译：嗜酸性粒细胞诱导DC成熟，调节免疫力。

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There are increased eosinophils in tumors, and they are generally associated with a good prognosis, whereas their presence in rejecting allografts is largely seen as a harbinger of poor outcome. The biologic role of eosinophils in their pathogenesis is more poorly understood than in allergy and asthma. Myeloid conventional dendritic cells (DCs) and conversely, plasmacytoid DCs are similarly associated with a good prognosis in cancer patients. We hypothesize that eosinophils, similar to NK cells, could mature DCs, and that could be responsible for regulating immunity in the setting of necrosis-associated chronic inflammation as occurs in cancer and transplant rejection. We have demonstrated that CpG DNA promotes eosinophil-induced DC maturation. As such, a greater linkage than had previously been considered between innate immune cells such as eosinophils and the adaptive immune response can be considered. Granulocytes were isolated from normal human whole blood by density gradient centrifugation followed by ammonium chloride-potassium lysis of the remaining red cells. Eosinophils were negatively separated using magnetic beads. Immature DCs were generated from CD-14 positively separated monocytes, which were cultured for 6 days with GM-CSF and IL-4. CpG ODN 2395 (CpG-C) as a pathogen-associated molecular pattern surrogate was used to induce eosinophil-based DC maturation. Transwells were used to assess cell-cell interaction between eosinophils and DCs. Eosinophil survival was assessed by flow cytometry; cells, which did not stain with Sytox-Orange, were considered viable. In the presence of CpG-C, eosinophils induced DC maturation. Similar results were obtained when eosinophils were pretreated with CpG for 4 h, washed, and cocultured afterwards with DCs. Eosinophil-induced maturation of DCs directly correlated with the eosinophil:DC ratio. Transwell studies showed that the direct cell-cell interaction between eosinophils and DCs enhances maturation. CpGs did not adversely affect eosinophil survival; thus, we could exclude the possibility that DC maturation was caused by sensing eosinophil cell death. While eosinophil-derived neurotoxin did not contribute to the described effect, DCs took up and internalized major basic protein (MBP), which was released from CpG-stimulated eosinophils, revealed by confocal imaging and flow cytometry. Thus, the DC maturational-inducing effect of eosinophils may be a result of released MBP from eosinophils. CpG-activated eosinophils mature conventional DCs. The role of viral or bacterial products or potentially, host-derived DNA as eosinophil activators with consequent DC maturation should be considered in more detail in the inflammatory settings in which eosinophils have been observed.
机译：肿瘤中的嗜酸性粒细胞增多，通常与良好的预后相关，而它们在排斥同种异体移植中的存在在很大程度上被认为是预后不良的预兆。与变态反应和哮喘相比，对嗜酸性粒细胞在其发病机理中的生物学作用了解得更少。髓样常规树突状细胞（DC），相反，浆细胞样DC与癌症患者的良好预后相似。我们假设，嗜酸性粒细胞与NK细胞类似，可以成熟DC，并且可以负责调节坏死相关的慢性炎症（如癌症和移植排斥）中的免疫力。我们已经证明，CpG DNA可以促进嗜酸性粒细胞诱导的DC成熟。这样，可以考虑比先天免疫细胞例如嗜酸性粒细胞和适应性免疫应答之间更大的连锁。通过密度梯度离心，然后氯化铵-钾裂解剩余的红细胞，从正常人全血中分离出粒细胞。使用磁珠将嗜酸性粒细胞阴性分离。从CD-14阳性分离的单核细胞生成未成熟的DC，将其与GM-CSF和IL-4培养6天。 CpG ODN 2395（CpG-C）作为病原体相关的分子模式替代物，用于诱导基于嗜酸性粒细胞的DC成熟。 Transwells用于评估嗜酸性粒细胞和DC之间的细胞间相互作用。通过流式细胞术评估嗜酸性粒细胞的存活。没有被Sytox-Orange染色的细胞被认为是可行的。在CpG-C存在下，嗜酸性粒细胞诱导DC成熟。当嗜酸性粒细胞用CpG预处理4小时，洗涤并随后与DC共培养时，获得了相似的结果。嗜酸性粒细胞诱导的DC成熟与嗜酸性粒细胞：DC比率直接相关。 Transwell研究表明，嗜酸性粒细胞和DC之间的直接细胞间相互作用增强了成熟度。 CpGs不会对嗜酸性粒细胞的存活产生不利影响。因此，我们可以排除DC成熟是由嗜酸性粒细胞死亡引起的。虽然嗜酸性粒细胞来源的神经毒素对所描述的作用没有贡献，但DC吸收并内化了主要碱性蛋白（MBP），该蛋白从CpG刺激的嗜酸性粒细胞中释放，通过共聚焦成像和流式细胞术揭示。因此，嗜酸性粒细胞DC成熟诱导作用可能是嗜酸性粒细胞释放MBP的结果。 CpG激活的嗜酸性粒细胞成熟了常规DC。在已观察到嗜酸性粒细胞的炎性环境中，应更详细地考虑病毒或细菌产物或潜在的宿主来源的DNA作为嗜酸性粒细胞活化剂并随之导致DC成熟的作用。

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