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首页> 外文期刊>Immunology: An Official Journal of the British Society for Immunology >Neonatal macrophages express elevated levels of interleukin-27 that oppose immune responses
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Neonatal macrophages express elevated levels of interleukin-27 that oppose immune responses

机译：新生儿巨噬细胞表达高水平的白细胞介素27，可抵抗免疫反应

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摘要

Microbial infections are a major cause of infant mortality worldwide because of impaired immune defences in this population. The nature of this work was to further understand the mechanistic limitations of the neonatal and infant immune response. Interleukin-27 (IL-27) is a heterodimeric cytokine of the IL-12 family that is produced primarily by antigen-presenting cells and is immunosuppressive toward a variety of immune cell types. We show that IL-27 gene expression is elevated in cord blood-derived macrophages relative to macrophages originating from healthy adults. We also evaluated the duration over which elevated IL-27 gene expression may impact immune responses in mice. Age-dependent analysis of IL-27 gene expression indicated that levels of IL-27 remained significantly elevated throughout infancy and then declined in adult mice. Flow cytometric analysis of intracellular cytokine-stained splenocytes further confirmed these results. Interleukin-27 may be induced during pregnancy to contribute to the immunosuppressive environment at the fetal-maternal interface because we demonstrate dose-responsive gene expression to progesterone in macrophages. Neutralization of IL-27 in neonatal macrophages improved the ability of these cells to limit bacterial replication. Moreover, neutralization of IL-27 during incubation with the Mycobacterium bovis bacillus Calmette-Guérin vaccine augmented the level of interferon-γ elicited from allogeneic CD4+ T lymphocytes. This suggests that blocking IL-27 during vaccination and infection may improve immune responses in newborn and infant populations.
机译：微生物感染是全世界婴儿死亡的主要原因，因为该人群的免疫防御能力受损。这项工作的本质是进一步了解新生儿和婴儿免疫反应的机制局限性。白介素27（IL-27）是IL-12家族的一种异二聚体细胞因子，主要由抗原呈递细胞产生，对多种免疫细胞类型具有免疫抑制作用。我们表明相对于健康成年人的巨噬细胞，脐血来源的巨噬细胞中IL-27基因表达升高。我们还评估了升高的IL-27基因表达可能影响小鼠免疫应答的持续时间。 IL-27基因表达的年龄依赖性分析表明，在整个婴儿期，IL-27的水平仍显着升高，然后在成年小鼠中降低。细胞内细胞因子染色的脾细胞的流式细胞术分析进一步证实了这些结果。在怀孕期间可能会诱导白介素27，以促进胎儿-母亲界面的免疫抑制环境，因为我们证明了巨噬细胞中孕激素的剂量反应性基因表达。新生儿巨噬细胞中IL-27的中和提高了这些细胞限制细菌复制的能力。此外，在与牛分枝杆菌卡介特-瓜林疫苗孵育期间中和IL-27会增加由同种CD4 + T淋巴细胞引起的干扰素-γ水平。这表明在疫苗接种和感染期间阻断IL-27可能会改善新生儿和婴儿群体的免疫反应。

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