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首页> 外文期刊>Immunology: An Official Journal of the British Society for Immunology >The Warburg effect in mycobacterial granulomas is dependent on the recruitment and activation of macrophages by interferon-gamma
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The Warburg effect in mycobacterial granulomas is dependent on the recruitment and activation of macrophages by interferon-gamma

机译：分枝肉芽肿中的沃堡效应取决于干扰素-γ对巨噬细胞的募集和激活

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摘要

Granulomas are the hallmark of mycobacterial disease. Here, we demonstrate that both the cell recruitment and the increased glucose consumption in granulomatous infiltrates during Mycobacterium avium infection are highly dependent on interferon-gamma (IFN-gamma). Mycobacterium avium-infected mice lacking IFN-gamma signalling failed to developed significant inflammatory infiltrations and lacked the characteristic uptake of the glucose analogue fluorine-18-fluorodeoxyglucose (FDG). To assess the role of macrophages in glucose uptake we infected mice with a selective impairment of IFN-gamma signalling in the macrophage lineage (MIIG mice). Although only a partial reduction of the granulomatous areas was observed in infected MIIG mice, the insensitivity of macrophages to IFN-gamma reduced the accumulation of FDG. In vivo, ex vivo and in vitro assays showed that macrophage activated by IFN-gamma displayed increased rates of glucose uptake and in vitro studies showed also that they had increased lactate production and increased expression of key glycolytic enzymes. Overall, our results show that the activation of macrophages by IFN-gamma is responsible for the Warburg effect observed in organs infected with M. avium.
机译：肉芽肿是分枝杆菌疾病的标志。在这里，我们证明了在鸟分枝杆菌感染期间肉芽肿浸润中的细胞募集和葡萄糖消耗的增加都高度依赖于干扰素-γ（IFN-γ）。缺乏IFN-γ信号传导的鸟分枝杆菌感染的小鼠未能发展出明显的炎症浸润，并且缺乏葡萄糖类似物氟-18-氟脱氧葡萄糖（FDG）的特征吸收。为了评估巨噬细胞在葡萄糖摄取中的作用，我们用巨噬细胞谱系中的IFN-γ信号传导的选择性损伤感染了小鼠（MIIG小鼠）。尽管在感染的MIIG小鼠中仅观察到肉芽肿区域的部分减少，但是巨噬细胞对IFN-γ的不敏感性降低了FDG的积累。体内，离体和体外测定表明，被IFN-γ激活的巨噬细胞显示出更高的葡萄糖摄取率，而体外研究也表明，它们具有增加的乳酸生成和关键的糖酵解酶表达。总体而言，我们的结果表明，IFN-γ激活巨噬细胞是在感染鸟分枝杆菌的器官中观察到的Warburg效应的原因。

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