Neutrophils are leukocytes that are capable of eliminating both intra‐ and extracellular pathogens by mechanisms such as phagocytosis, degranulation, and release of neutrophil extracellular traps (NETs). Histoplasma capsulatum var. capsulatum (H . capsulatum ) is a dimorphic fungus with a global distribution that causes histoplasmosis, a disease that is endemic in different geographic areas and is spreading worldwide. The release of NETs has been described as an important host defense mechanism against different fungi; however, there are no reports demonstrating that this process is implicated in neutrophil response to H . capsulatum infection. Therefore, the aim of this work is to investigate whether isolated human neutrophils release NETs in response to H . capsulatum and the potential mechanisms involved, as well as delineate the NETs antifungal activity. Using both confocal fluorescence and scanning electron microscopy techniques, we determined that NETs are released in vitro in response to H . capsulatum via an oxidative mechanism that is downstream of activation of the Syk and Src kinase pathways and is also dependent on CD18. NETs released in response to H . capsulatum yeasts involve the loss of neutrophil viability and are associated with elastase and citrullinated histones, however also can occur in a PAD4 histone citrullination independent pathway. This NETs also presented fungicidal activity against H . capsulatum yeasts. Our findings may contribute to the understanding of how neutrophils recognize and respond as immune effector cells to H . capsulatum , which may lead to better knowledge of histoplasmosis pathophysiology and treatment.

中文翻译：

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在人嗜中性粒细胞中组织胞浆囊膜诱导的细胞外DNA陷阱释放。

中性粒细胞是白细胞，能够通过吞噬作用，脱粒和中性粒细胞外陷阱（NETs）释放等机制消除细胞内和细胞外病原体。荚膜组织胞浆菌变种。荚膜（^ h。荚膜）是一种双态性真菌具有全球分布，导致组织胞浆菌病，一病就是在不同的地理区域流行和正在全球蔓延。NET的发布被描述为针对不同真菌的重要宿主防御机制。但是，没有报道表明该过程与嗜中性白细胞对H的反应有关。囊状感染。因此，这项工作的目的是研究分离的人类嗜中性粒细胞是否响应H释放NETs 。囊膜及其潜在的机制，以及NETs的抗真菌活性。使用共聚焦荧光和扫描电子显微镜技术，我们确定NETs在体外响应H释放。荚膜通过氧化机制，是的Syk和Src激酶途径激活的下游，并且还依赖于CD18。母语响应发布^ h。囊状酵母涉及嗜中性粒细胞活力的丧失，并且与弹性蛋白酶和瓜氨酸化的组蛋白有关，但是也可以在PAD4组蛋白瓜氨酸化独立途径中发生。该NETs还呈现出针对H的杀真菌活性。荚膜酵母。我们的发现可能有助于了解中性粒细胞如何识别和响应H的免疫效应细胞。荚膜，这可能导致组织胞浆菌病的病理生理和治疗有了更好的了解。