Human leukocytes kill Aspergillus nidulans by reactive oxygen species-independent mechanisms

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

Research output: Contribution to journalArticle

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Abstract

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.
Original languageEnglish
Pages (from-to)767-773
Number of pages7
JournalInfection and Immunity
Volume79
Issue number2
Early online date15 Nov 2010
DOIs
Publication statusPublished - Feb 2011

Fingerprint

Chronic Granulomatous Disease
Aspergillus nidulans
Reactive Oxygen Species
Leukocytes
Aspergillus fumigatus
NADPH Oxidase
Neutrophils
Alveolar Macrophages
Blood Cells
Aspergillosis
Hyphae
Aspergillus
Germination
Infection
Innate Immunity
Fungi

Keywords

  • animals
  • Aspergillus nidulans
  • female
  • humans
  • hydrogen peroxide
  • hyphae
  • leukocytes, mononuclear
  • male
  • membrane glycoproteins
  • mice
  • NADPH oxidase
  • neutrophils
  • reactive oxygen species

Cite this

Henriet, S. S. V., Hermans, P. W. M., Verweij, P. E., Simonetti, E., Holland, S. M., Sugui, J. A., ... Warris, A. (2011). Human leukocytes kill Aspergillus nidulans by reactive oxygen species-independent mechanisms. Infection and Immunity, 79(2), 767-773. https://doi.org/10.1128/IAI.00921-10

Human leukocytes kill Aspergillus nidulans by reactive oxygen species-independent mechanisms. / Henriet, Stefanie S. V.; Hermans, Peter W. M.; Verweij, Paul E.; Simonetti, Elles; Holland, Steven M.; Sugui, Janyce A.; Kwon-Chung, Kyung J.; Warris, Adilia.

In: Infection and Immunity, Vol. 79, No. 2, 02.2011, p. 767-773.

Research output: Contribution to journalArticle

Henriet, SSV, Hermans, PWM, Verweij, PE, Simonetti, E, Holland, SM, Sugui, JA, Kwon-Chung, KJ & Warris, A 2011, 'Human leukocytes kill Aspergillus nidulans by reactive oxygen species-independent mechanisms', Infection and Immunity, vol. 79, no. 2, pp. 767-773. https://doi.org/10.1128/IAI.00921-10
Henriet SSV, Hermans PWM, Verweij PE, Simonetti E, Holland SM, Sugui JA et al. Human leukocytes kill Aspergillus nidulans by reactive oxygen species-independent mechanisms. Infection and Immunity. 2011 Feb;79(2):767-773. https://doi.org/10.1128/IAI.00921-10
Henriet, Stefanie S. V. ; Hermans, Peter W. M. ; Verweij, Paul E. ; Simonetti, Elles ; Holland, Steven M. ; Sugui, Janyce A. ; Kwon-Chung, Kyung J. ; Warris, Adilia. / Human leukocytes kill Aspergillus nidulans by reactive oxygen species-independent mechanisms. In: Infection and Immunity. 2011 ; Vol. 79, No. 2. pp. 767-773.
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