PMID- 29248928 OWN - NLM STAT- MEDLINE DCOM- 20190909 LR - 20210109 IS - 1662-8128 (Electronic) IS - 1662-811X (Print) IS - 1662-811X (Linking) VI - 10 IP - 2 DP - 2018 TI - Differential Kinetics of Aspergillus nidulans and Aspergillus fumigatus Phagocytosis. PG - 145-160 LID - 10.1159/000484562 [doi] AB - 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. CI - The Author(s). Published by S. Karger AG, Basel. FAU - Gresnigt, Mark S AU - Gresnigt MS AD - Medical Research Council Centre for Medical Mycology at the University of Aberdeen, Aberdeen Fungal Group, Institute of Medical Sciences, University of Aberdeen, Aberdeen, UK. FAU - Becker, Katharina L AU - Becker KL FAU - Leenders, Floris AU - Leenders F FAU - Alonso, M Fernanda AU - Alonso MF FAU - Wang, Xiaowen AU - Wang X FAU - Meis, Jacques F AU - Meis JF FAU - Bain, Judith M AU - Bain JM FAU - Erwig, Lars P AU - Erwig LP FAU - van de Veerdonk, Frank L AU - van de Veerdonk FL LA - eng GR - MR/N006364/1/MRC_/Medical Research Council/United Kingdom PT - Comparative Study PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20171216 PL - Switzerland TA - J Innate Immun JT - Journal of innate immunity JID - 101469471 RN - 0 (Cytokines) RN - 0 (Reactive Oxygen Species) SB - IM MH - Animals MH - Aspergillosis/immunology/microbiology MH - Aspergillus fumigatus/*immunology MH - Aspergillus nidulans/*immunology MH - Cell Line MH - Cell Movement MH - Cytokines/metabolism MH - Granulomatous Disease, Chronic/immunology/microbiology MH - Humans MH - Kinetics MH - Leukocytes, Mononuclear/metabolism/microbiology MH - Macrophages/metabolism/microbiology MH - Mice MH - *Phagocytosis MH - Phagosomes/metabolism/microbiology MH - Reactive Oxygen Species/metabolism MH - Species Specificity PMC - PMC6757152 OTO - NOTNLM OT - Aspergillus fumigatus OT - Aspergillus nidulans OT - Chronic granulomatous disease OT - LC3-associated phagocytosis OT - Phagocytosis OT - Phagosome acidification EDAT- 2017/12/19 06:00 MHDA- 2019/09/10 06:00 PMCR- 2017/12/16 CRDT- 2017/12/18 06:00 PHST- 2017/04/07 00:00 [received] PHST- 2017/10/25 00:00 [accepted] PHST- 2017/12/19 06:00 [pubmed] PHST- 2019/09/10 06:00 [medline] PHST- 2017/12/18 06:00 [entrez] PHST- 2017/12/16 00:00 [pmc-release] AID - 000484562 [pii] AID - jin-0010-0145 [pii] AID - 10.1159/000484562 [doi] PST - ppublish SO - J Innate Immun. 2018;10(2):145-160. doi: 10.1159/000484562. Epub 2017 Dec 16.