Reactive oxygen species produced by the NADPH oxidase 2 complex in monocytes protect mice from bacterial infections.
Reactive oxygen species produced by the NADPH oxidase 2 complex in monocytes protect mice from bacterial infections.
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DOI：
10.4049/jimmunol.1103430
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发表时间：
2012-05-15
期刊：
影响因子：
--
通讯作者：
Holmdahl R
中科院分区：
文献类型：
--
作者：
Pizzolla A;Hultqvist M;Nilson B;Grimm MJ;Eneljung T;Jonsson IM;Verdrengh M;Kelkka T;Gjertsson I;Segal BH;Holmdahl R
慢性肉芽肿病(CGD)是一种遗传性疾病，其特征是反复发生危及生命的细菌和真菌感染。CGD是由于编码NADPH氧化酶2(NOX2)复合亚单位的基因突变导致吞噬细胞产生活性氧物种(ROS)的缺陷所致。编码NOX2亚单位NCF1(P47Phox)的Ncf1基因自发突变的小鼠，吞噬细胞NOX2活性有缺陷。这些小鼠偶尔会受到木质葡萄球菌或常见的CGD病原体金黄色葡萄球菌的局部自发性感染。NCF1突变小鼠比野生型小鼠更容易受到这些细菌的全身攻击。在人CD68启动子下携带野生型Ncf1基因的转基因突变小鼠(MN+小鼠)在单核/巨噬细胞中获得了NCF1的表达和功能上的NOX2活性，但在一些被定义为中性粒细胞的CD11b+Ly6G+细胞中也检测到了极低的NOX2活性。与MN−小鼠相比，MN+小鼠不发生自发感染，并且对葡萄球菌感染具有更强的抵抗力。最引人注目的是，MN+小鼠在注射洋葱伯克霍尔德氏菌后存活，而MN−小鼠死亡。洋葱伯克霍尔德氏菌是慢性萎缩性胃病患者的一种条件致病菌。因此，单核/巨噬细胞表达功能性NCF1可以保护机体免受自发性和感染性细菌感染。
Chronic granulomatous disease (CGD) is an inherited disorder characterized by recurrent life-threatening bacterial and fungal infections. CGD results from defective production of reactive oxygen species (ROS) by phagocytes caused by mutations in genes encoding the NADPH oxidase 2 (NOX2) complex subunits. Mice with a spontaneous mutation in Ncf1, which encodes the NCF1 (p47phox) subunit of NOX2, have defective phagocyte NOX2 activity. These mice occasionally develop local spontaneous infections by Staphylococcus xylosus or by the common CGD pathogen S. aureus. Ncf1 mutant mice were more susceptible to systemic challenge with these bacteria than wild type mice. Transgenic Ncf1 mutant mice harboring wild type Ncf1 gene under the human CD68 promoter (MN+ mice) gained the expression of NCF1 and functional NOX2 activity specifically in monocyte/macrophages, although minimal NOX2 activity was detected also in some CD11b+Ly6G+ cells defined as neutrophils. MN+ mice did not develop spontaneous infection and were more resistant to administered staphylococcal infections compared to MN− mice. Most strikingly, MN+ mice survived after administered Burkholderia cepacia, an opportunistic pathogen in CGD patients, whereas MN− mice died. Thus, monocyte/macrophage expression of functional NCF1 protected against spontaneous and administered bacterial infections.
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影响因子：
7.4
作者：
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通讯作者：
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影响因子：
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影响因子：
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作者：
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