| Human leukocytes kill Aspergillus nidulans by reactive oxygen species-independent mechanisms. | |
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MedLine Citation:
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PMID: 21078850 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Invasive aspergillosis is a major threat for patients suffering from chronic granulomatous disease (CGD). Although Aspergillus fumigatus is the most commonly encountered Aspergillus species, the presence of A. nidulans appears to be disproportionately high in CGD patients. The purpose of this study was to investigate the involvement of the NADPH oxidase and the resulting reactive oxygen species (ROS) in host defense against fungi and to clarify their relationship toward A. nidulans. Murine CGD alveolar macrophages (AM) and polymorphonuclear leukocytes (PMN) and peripheral blood mononuclear cells (PBMC) from healthy controls and CGD patients were challenged with either A. fumigatus or A. nidulans. Analysis of the antifungal effects of ROS revealed that A. nidulans, in contrast to A. fumigatus, is not susceptible to ROS. In addition, infection with live A. nidulans did not result in any measurable ROS release. Remarkably, human CGD PMN and PBMC and murine CGD AM were at least equipotent at arresting conidial germination compared to healthy controls. Blocking of the NADPH oxidase resulted in significantly reduced damage of A. fumigatus but did not affect A. nidulans hyphae. Furthermore, the microbicidal activity of CGD PMN was maintained toward A. nidulans but not A. fumigatus. In summary, antifungal resistance to A. nidulans is not directly ROS related. The etiology of A. nidulans infections in CGD cannot be explained by the simple absence of the direct microbicidal effect of ROS. In vivo, the NADPH oxidase is a critical regulator of innate immunity whose unraveling will improve our understanding of fungal pathogenesis in CGD. |
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Authors:
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Stefanie S V Henriet; Peter W M Hermans; Paul E Verweij; Elles Simonetti; Steven M Holland; Janyce A Sugui; Kyung J Kwon-Chung; Adilia Warris |
Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Intramural; Research Support, Non-U.S. Gov't Date: 2010-11-15 |
Journal Detail:
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Title: Infection and immunity Volume: 79 ISSN: 1098-5522 ISO Abbreviation: Infect. Immun. Publication Date: 2011 Feb |
Date Detail:
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Created Date: 2011-01-24 Completed Date: 2011-03-15 Revised Date: 2011-08-03 |
Medline Journal Info:
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Nlm Unique ID: 0246127 Medline TA: Infect Immun Country: United States |
Other Details:
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Languages: eng Pagination: 767-73 Citation Subset: IM |
Affiliation:
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Department of Pediatrics, Radboud University Nijmegen Medical Centre, Nijmegen, Netherlands. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Aspergillus nidulans / immunology* Female Humans Hydrogen Peroxide Hyphae / drug effects Leukocytes, Mononuclear / physiology* Male Membrane Glycoproteins / genetics, metabolism Mice NADPH Oxidase / antagonists & inhibitors, genetics, metabolism Neutrophils / physiology* Reactive Oxygen Species |
| Chemical | |
Reg. No./Substance:
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0/Membrane Glycoproteins; 0/Reactive Oxygen Species; 7722-84-1/Hydrogen Peroxide; EC 1.6.3.1/Cybb protein, mouse; EC 1.6.3.1/NADPH Oxidase |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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