Aspergillus fumigatus is a filamentous fungus which can cause multiple diseases in humans. Allergic broncho-pulmonary aspergillosis (ABPA) is a disease diagnosed primarily in cystic fibrosis patients caused by a severe allergic response often to long-term A. fumigatus colonization in the lungs. Mice develop an allergic response to repeated inhalation of A. fumigatus spores; however, no strains have been identified that can survive long-term in the mouse lung and cause ABPA-like disease. We characterized A. fumigatus strain W72310, which was isolated from the expectorated sputum of an ABPA patient, by whole-genome sequencing and in vitro and in vivo viability assays in comparison to a common reference strain, CEA10. W72310 was resistant to leukocyte-mediated killing and persisted in the mouse lung longer than CEA10, a phenotype that correlated with greater resistance to oxidative stressors, hydrogen peroxide, and menadione, in vitro. In animals both sensitized and challenged with W72310, conidia, but not hyphae, were viable in the lungs for up to 21 days in association with eosinophilic airway inflammation, airway leakage, serum IgE, and mucus production. W72310-sensitized mice that were recall challenged with conidia had increased inflammation, Th1 and Th2 cytokines, and airway leakage compared to controls. Collectively, our studies demonstrate that a unique strain of A. fumigatus resistant to leukocyte killing can persist in the mouse lung in conidial form and elicit features of ABPA-like disease.

中文翻译：

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烟曲霉菌株特异性分生孢子肺部持久性导致过敏性支气管肺曲霉病样疾病表型


烟曲霉是一种丝状真菌，可引起人类多种疾病。过敏性支气管肺曲霉病 (ABPA) 是一种主要在囊性纤维化患者中诊断的疾病，通常由烟曲霉在肺部长期定植引起的严重过敏反应引起。小鼠反复吸入烟曲霉孢子后会产生过敏反应；然而，尚未发现任何菌株可以在小鼠肺部长期存活并引起类似 ABPA 的疾病。我们通过全基因组测序以及体外和体内活力测定，与常见参考菌株 CEA10 进行比较，对烟曲霉菌株 W72310 进行了表征，该菌株是从 ABPA 患者的痰液中分离出来的。 W72310 对白细胞介导的杀伤具有抵抗力，并且在小鼠肺中的持续时间比 CEA10 更长，这种表型与体外对氧化应激物、过氧化氢和甲萘醌的更强抵抗力相关。在用 W72310 致敏和攻击的动物中，分生孢子（而非菌丝）在肺部存活长达 21 天，与嗜酸性气道炎症、气道渗漏、血清 IgE 和粘液产生相关。与对照组相比，接受分生孢子攻击的 W72310 致敏小鼠炎症、Th1 和 Th2 细胞因子以及气道渗漏增加。总的来说，我们的研究表明，一种对白细胞杀伤具有抗性的烟曲霉独特菌株可以以分生孢子形式持续存在于小鼠肺部，并引发 ABPA 样疾病的特征。