Neutrophils are primary phagocytes of the innate immune system that generate reactive oxygen species (ROS) and mediate host defense. Deficient phagocyte NADPH oxidase (PHOX) function leads to chronic granulomatous disease (CGD) that is characterized by invasive infections, including those by the generally non-pathogenic fungus Aspergillus nidulans The role of neutrophil ROS in this specific host-pathogen interaction remains unclear. Here, we exploit the optical transparency of zebrafish to image the effects of neutrophil ROS on invasive fungal growth and neutrophil behavior in response to Aspergillus nidulans In a wild-type host, A. nidulans germinates rapidly and elicits a robust inflammatory response with efficient fungal clearance. PHOX-deficient larvae have increased susceptibility to invasive A. nidulans infection despite robust neutrophil infiltration. Expression of subunit p22phox (officially known as CYBA), specifically in neutrophils, does not affect fungal germination but instead limits the area of fungal growth and excessive neutrophil inflammation and is sufficient to restore host survival in p22phox-deficient larvae. These findings suggest that neutrophil ROS limits invasive fungal growth and has immunomodulatory activities that contribute to the specific susceptibility of PHOX-deficient hosts to invasive A. nidulans infection.

中文翻译：

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中性粒细胞吞噬细胞氧化酶活性控制斑马鱼的侵袭性真菌生长和炎症。

中性粒细胞是先天免疫系统的主要吞噬细胞，可产生活性氧（ROS）并介导宿主防御。吞噬细胞NADPH氧化酶（PHOX）的功能不足会导致慢性肉芽肿病（CGD），其特征是侵入性感染，包括一般非致病性真菌构巢曲霉（Aspergillus nidulans）的侵染。在这里，我们利用斑马鱼的光学透明度来成像中性粒细胞ROS对侵染性真菌生长和嗜中性粒细胞行为的响应，以应对构巢曲霉。在野生型宿主中，构巢曲霉迅速发芽，并通过有效的真菌清除作用引发强烈的炎症反应。缺乏PHOX的幼虫对侵袭性A的敏感性增加。嗜中性粒细胞浸润尽管强烈，但尼杜兰感染。p22phox亚基（正式称为CYBA）的表达，特别是在嗜中性粒细胞中的表达，不会影响真菌的萌发，反而会限制真菌的生长和嗜中性粒细胞的过度炎症，并足以恢复缺乏p22phox的幼虫的宿主存活。这些发现表明，嗜中性白细胞ROS限制了侵袭性真菌的生长，并具有免疫调节活性，这些活性有助于PHOX缺陷宿主对侵袭性构巢曲霉感染的特异性敏感性。