Differential Kinetics of Aspergillus nidulans and Aspergillus fumigatus Phagocytosis.
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.
['Gresnigt|Mark S|MS|', 'Becker|Katharina L|KL|', 'Leenders|Floris|F|', 'Alonso|M Fernanda|MF|', 'Wang|Xiaowen|X|', 'Meis|Jacques F|JF|', 'Bain|Judith M|JM|', 'Erwig|Lars P|LP|', 'van de Veerdonk|Frank L|FL|']
D000818:Animals D001228:Aspergillosis D001232:Aspergillus fumigatus D001233:Aspergillus nidulans D002460:Cell Line D002465:Cell Movement D016207:Cytokines D006105:Granulomatous Disease, Chronic D006801:Humans D007700:Kinetics D007963:Leukocytes, Mononuclear D008264:Macrophages D051379:Mice D010587:Phagocytosis D010588:Phagosomes D017382:Reactive Oxygen Species D013045:Species Specificity
Phagocytosis Chronic granulomatous disease Phagosome acidification LC3-associated phagocytosis <italic>Aspergillus fumigatus</italic> <italic>Aspergillus nidulans</italic>