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

doi:10.1159/000484562

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 language	English
Pages (from-to)	145-160
Number of pages	16
Journal	Journal of Innate Immunity
Volume	10
Issue number	2
Early online date	16 Dec 2017
DOIs	https://doi.org/10.1159/000484562
Publication status	Published - Mar 2018

Bibliographical note

Acknowledgements:
The authors would like to acknowledge Fraser P. Coxon and Ian Ganley for providing LC3-GFP-mCherry BMDMs. M.S.G. was supported by an FEMS research grant and F.L.v.d.V. was supported by ZonMW under the name EURO-CMC frame of E-Rare-2, the ERA-Net for Research on Rare Diseases.

Keywords

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

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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Differential Kinetics of Aspergillus nidulans
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Cite this

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title = "Differential Kinetics of Aspergillus nidulans and Aspergillus fumigatus Phagocytosis",

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

note = "Acknowledgements: The authors would like to acknowledge Fraser P. Coxon and Ian Ganley for providing LC3-GFP-mCherry BMDMs. M.S.G. was supported by an FEMS research grant and F.L.v.d.V. was supported by ZonMW under the name EURO-CMC frame of E-Rare-2, the ERA-Net for Research on Rare Diseases.",

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doi = "10.1159/000484562",

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AU - Gresnigt, Mark S

AU - Becker, Katharina L

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AU - Alonso, M Fernanda

AU - Wang, Xiaowen

AU - Meis, Jacques F

AU - Bain, Judith M

AU - Erwig, Lars P

AU - van de Veerdonk, Frank L

N1 - Acknowledgements: The authors would like to acknowledge Fraser P. Coxon and Ian Ganley for providing LC3-GFP-mCherry BMDMs. M.S.G. was supported by an FEMS research grant and F.L.v.d.V. was supported by ZonMW under the name EURO-CMC frame of E-Rare-2, the ERA-Net for Research on Rare Diseases.

PY - 2018/3

Y1 - 2018/3

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.

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.

KW - Aspergillus fumigatus

KW - Aspergillus nidulans

KW - phagocytosis

KW - Phagosome acidification

KW - LC3-associated phagocytosis

KW - Chronic granulomatous disease

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DO - 10.1159/000484562

M3 - Article

C2 - 29248928

SN - 1662-811X

VL - 10

SP - 145

EP - 160

JO - Journal of Innate Immunity

JF - Journal of Innate Immunity

IS - 2

ER -

Differential Kinetics of Aspergillus nidulans and Aspergillus fumigatus Phagocytosis

Abstract

Bibliographical note

Keywords

UN SDGs

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