Medical Research Council Centre for Medical Mycology at the University of Aberdeen, Aberdeen Fungal Group, Institute of Medical Sciences, University of Aberdeen, Aberdeen, UK.
J Innate Immun. 2018;10(2):145-160. doi: 10.1159/000484562. Epub 2017 Dec 16.
Invasive aspergillosis mainly occurs in immunocompromised patients and is commonly caused by Aspergillus fumigatus, while A.nidulans is rarely the causative agent. However, in chronic granulomatous disease (CGD) patients, A. nidulans is a frequent cause of invasive aspergillosis and is associated with higher mortality. Immune recognition of A. nidulans was compared to A. fumigatus to offer an insight into why A. nidulans infections are prevalent in CGD. Live cell imaging with J774A.1 macrophage-like cells and LC3-GFP-mCherry bone marrow-derived macrophages (BMDMs) revealed that phagocytosis of A. nidulans was slower compared to A. fumigatus. This difference could be attributed to slower migration of J774A.1 cells and a lower percentage of migrating BMDMs. In addition, delayed phagosome acidification and LC3-associated phagocytosis was observed with A. nidulans. Cytokine and oxidative burst measurements in human peripheral blood mononuclear cells revealed a lower oxidative burst upon challenge with A. nidulans. In contrast, A. nidulans induced significantly higher concentrations of cytokines. Collectively, our data demonstrate that A. nidulans is phagocytosed and processed at a slower rate compared to A. fumigatus, resulting in reduced fungal killing and increased germination of conidia. This slower rate of A. nidulans clearance may be permissive for overgrowth within certain immune settings.
侵袭性曲霉病主要发生于免疫功能低下的患者，通常由烟曲霉引起，而构巢曲霉很少是致病因素。然而，在慢性肉芽肿病（CGD）患者中，构巢曲霉是侵袭性曲霉病的常见病因，与更高的死亡率相关。我们比较了对构巢曲霉和烟曲霉的免疫识别，以深入了解为什么 CGD 患者中构巢曲霉感染很普遍。使用 J774A.1 巨噬样细胞和 LC3-GFP-mCherry 骨髓来源巨噬细胞（BMDM）进行活细胞成像，结果显示与烟曲霉相比，构巢曲霉的吞噬作用较慢。这种差异可能归因于 J774A.1 细胞迁移速度较慢，以及迁移的 BMDM 百分比较低。此外，我们观察到构巢曲霉的吞噬体酸化和 LC3 相关吞噬作用延迟。在人外周血单核细胞中进行细胞因子和氧化爆发测量，结果显示在受到构巢曲霉的挑战时，氧化爆发较低。相比之下，构巢曲霉诱导的细胞因子浓度显著更高。总的来说，我们的数据表明，与烟曲霉相比，构巢曲霉的吞噬作用和处理速度较慢，导致真菌杀伤减少和孢子发芽增加。这种较慢的构巢曲霉清除率可能在某些免疫环境下有利于过度生长。
