Restoration of NET formation by gene therapy in CGD controls aspergillosis
Restoration of NET formation by gene therapy in CGD controls aspergillosis
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DOI：
10.1182/blood-2009-05-221606
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发表时间：
2009-09-24
期刊：
影响因子：
20.3
通讯作者：
Reichenbach, Janine
中科院分区：
文献类型：
--
作者：
Bianchi, Matteo;Hakkim, Abdul;Reichenbach, Janine
慢性肉芽肿病（CGD）患者的烟酰胺腺嘌呤二核苷酸磷酸（NADPH）氧化酶功能受损，导致中性粒细胞的抗菌活性较差，包括无法产生中性粒细胞细胞外陷阱（NET）。侵袭性曲霉病是CGD患者死亡的主要原因;目前尚不清楚中性粒细胞如何控制健康人的曲霉菌。本研究的目的是确定基因治疗是否通过补充NADPH氧化酶功能恢复CGD中的NET形成，以及NET是否对构巢曲霉具有抗菌活性。在这里，我们表明，重建NET形成的CGD患者的基因治疗恢复中性粒细胞消除构巢曲霉分生孢子和菌丝，并与快速治愈既存的治疗难治性侵袭性肺曲霉病，强调作用的功能性NADPH氧化酶在NET的形成和抗真菌活性。（血。2009; 114：2619-2622）
Chronic granulomatous disease (CGD) patients have impaired nicotinamide adenine dinucleotide phosphate (NADPH) oxidase function, resulting in poor antimicrobial activity of neutrophils, including the inability to generate neutrophil extracellular traps (NETs). Invasive aspergillosis is the leading cause of death in patients with CGD; it is unclear how neutrophils control Aspergillus species in healthy persons. The aim of this study was to determine whether gene therapy restores NET formation in CGD by complementation of NADPH oxidase function, and whether NETs have antimicrobial activity against Aspergillus nidulans. Here we show that reconstitution of NET formation by gene therapy in a patient with CGD restores neutrophil elimination of A nidulans conidia and hyphae and is associated with rapid cure of preexisting therapy refractory invasive pulmonary aspergillosis, underlining the role of functional NADPH oxidase in NET formation and antifungal activity. (Blood. 2009; 114: 2619-2622)