Differential Kinetics of Aspergillus nidulans and Aspergillus fumigatus Phagocytosis

Mark S Gresnigt, Katharina L Becker, Floris Leenders, M Fernanda Alonso, Xiaowen Wang, Jacques F Meis, Judith M Bain, Lars P Erwig, Frank L van de Veerdonk

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Abstract

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.

Original languageEnglish
Pages (from-to)145-160
Number of pages16
JournalJournal of Innate Immunity
Volume10
Issue number2
Early online date16 Dec 2017
DOIs
Publication statusPublished - Mar 2018

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Aspergillus nidulans
Aspergillus fumigatus
Phagocytosis
Chronic Granulomatous Disease
Aspergillosis
Respiratory Burst
Macrophages
Cytokines
Phagosomes
Fungal Spores
Immunocompromised Host
Germination
Cell Movement
Blood Cells
Mortality

Keywords

  • Aspergillus fumigatus
  • Aspergillus nidulans
  • phagocytosis
  • Phagosome acidification
  • LC3-associated phagocytosis
  • Chronic granulomatous disease

Cite this

Gresnigt, M. S., Becker, K. L., Leenders, F., Alonso, M. F., Wang, X., Meis, J. F., ... van de Veerdonk, F. L. (2018). Differential Kinetics of Aspergillus nidulans and Aspergillus fumigatus Phagocytosis. Journal of Innate Immunity, 10(2), 145-160. https://doi.org/10.1159/000484562

Differential Kinetics of Aspergillus nidulans and Aspergillus fumigatus Phagocytosis. / Gresnigt, Mark S; Becker, Katharina L; Leenders, Floris; Alonso, M Fernanda; Wang, Xiaowen; Meis, Jacques F; Bain, Judith M; Erwig, Lars P; van de Veerdonk, Frank L.

In: Journal of Innate Immunity, Vol. 10, No. 2, 03.2018, p. 145-160.

Research output: Contribution to journalArticle

Gresnigt, MS, Becker, KL, Leenders, F, Alonso, MF, Wang, X, Meis, JF, Bain, JM, Erwig, LP & van de Veerdonk, FL 2018, 'Differential Kinetics of Aspergillus nidulans and Aspergillus fumigatus Phagocytosis', Journal of Innate Immunity, vol. 10, no. 2, pp. 145-160. https://doi.org/10.1159/000484562
Gresnigt MS, Becker KL, Leenders F, Alonso MF, Wang X, Meis JF et al. Differential Kinetics of Aspergillus nidulans and Aspergillus fumigatus Phagocytosis. Journal of Innate Immunity. 2018 Mar;10(2):145-160. https://doi.org/10.1159/000484562
Gresnigt, Mark S ; Becker, Katharina L ; Leenders, Floris ; Alonso, M Fernanda ; Wang, Xiaowen ; Meis, Jacques F ; Bain, Judith M ; Erwig, Lars P ; van de Veerdonk, Frank L. / Differential Kinetics of Aspergillus nidulans and Aspergillus fumigatus Phagocytosis. In: Journal of Innate Immunity. 2018 ; Vol. 10, No. 2. pp. 145-160.
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abstract = "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.",
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N2 - 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.

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