Cytokines Involved in Interferon-γ Production by Human Macrophages
Cytokines Involved in Interferon-γ Production by Human Macrophages
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DOI：
10.1159/000247156
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发表时间：
2010-01-01
影响因子：
5.3
通讯作者：
Nau, Gerard J.
中科院分区：
文献类型：
--
作者：
Robinson, Cory M.;O'Dee, Dawn;Nau, Gerard J.
干扰素(IFN)- γ对细胞内病原体的免疫防御，特别是巨噬细胞控制结核分枝杆菌（MTB）的能力非常重要。越来越多的证据支持巨噬细胞产生ifn - γ的观点。我们在这里描述了细胞因子的相互作用，决定ifn - γ的表达和分泌在结核分枝杆菌感染的人巨噬细胞。检测mtb感染的人巨噬细胞培养上清中具有重要生物学意义的ifn - γ水平需要添加白细胞介素(IL)-12。IL-18增强了人巨噬细胞对MTB和补充IL-12联合作用的ifn - γ产生。虽然IL-18基因表达总体上保持不变，但MTB和IL-12的联合作用增强了IL-18蛋白的分泌，其主要作用是刺激ifn - γ的释放。重要的是，MTB感染诱导的IL-27通过拮抗人巨噬细胞中的IL-18活性来抑制ifn - γ的产生。IL-27的中和增加了IL-18受体p链的表达。此外，IL-27阻断NF-kappa B对IL-18的激活。这些结果确定了人类巨噬细胞产生ifn - γ所需的信号，并强调了结核分枝杆菌感染期间产生的细胞因子之间的相互作用。他们共同确定了IL-27通过破坏IL-18活性来调节巨噬细胞功能的新作用。版权所有(C) 2009 S. Karger AG，巴塞尔
Interferon (IFN)-gamma is important to the immune defense against intracellular pathogens and specifically the ability of macrophages to control Mycobocterium tuberculosis (MTB). Increasing evidence has accumulated to support the idea that macrophages produce IFN-gamma. We describe here the cytokine interactions that determine IFN-gamma expression and secretion during MTB infection of human macrophages. Detection of biologically important IFN-gamma levels in culture supernatants of MTB-infected human macrophages requires the addition of interleukin (IL)-12. IL-18 augmented IFN-gamma production from human macrophages in response to the combination of MTB and supplemental IL-12. Although IL-18 gene expression was generally unchanged, IL-18 protein secretion was enhanced by the combination of MTB and IL-12, and functioned primarily to stimulate IFN-gamma release. Importantly, IL-27 induced by MTB infection opposed IFN-gamma production by antagonizing IL-18 activity in human macrophages. Neutralization of IL-27 increased the expression of the IL-18 receptor P-chain. Additionally, IL-27 blocked NF-kappa B activation in response to IL-18. These results define the signals required for IFN-gamma production by human macrophages and highlight the interactions between cytokines produced during MTB infection. Together, they identify a novel role for IL-27 in regulating macrophage function by disrupting IL-18 activity. Copyright (C) 2009 S. Karger AG, Basel