Neuraminidase and SIGLEC15 modulate the host defense against pulmonary aspergillosis
Summary: Influenza-associated pulmonary aspergillosis (IAPA) has been reported increasingly since the advent of use of neuraminidase (NA) inhibitors following the 2009 influenza pandemic. We hypothesize that blocking host NA modulates the immune response against Aspergillus fumigatus. We demonstrate...
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Elsevier
2021-05-01
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Series: | Cell Reports Medicine |
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Online Access: | http://www.sciencedirect.com/science/article/pii/S2666379121001178 |
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Article |
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DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Intan M.W. Dewi Cristina Cunha Martin Jaeger Mark S. Gresnigt Marina E. Gkountzinopoulou Fadel M. Garishah Cláudio Duarte-Oliveira Cláudia F. Campos Lore Vanderbeke Agustin Resendiz Sharpe Roger J. Brüggemann Paul E. Verweij Katrien Lagrou Greetje Vande Velde Quirijn de Mast Leo A.B. Joosten Mihai G. Netea Andre J.A.M. van der Ven Joost Wauters Agostinho Carvalho Frank L. van de Veerdonk |
spellingShingle |
Intan M.W. Dewi Cristina Cunha Martin Jaeger Mark S. Gresnigt Marina E. Gkountzinopoulou Fadel M. Garishah Cláudio Duarte-Oliveira Cláudia F. Campos Lore Vanderbeke Agustin Resendiz Sharpe Roger J. Brüggemann Paul E. Verweij Katrien Lagrou Greetje Vande Velde Quirijn de Mast Leo A.B. Joosten Mihai G. Netea Andre J.A.M. van der Ven Joost Wauters Agostinho Carvalho Frank L. van de Veerdonk Neuraminidase and SIGLEC15 modulate the host defense against pulmonary aspergillosis Cell Reports Medicine aspergillosis neuraminidase oseltamivir SIGLEC15 |
author_facet |
Intan M.W. Dewi Cristina Cunha Martin Jaeger Mark S. Gresnigt Marina E. Gkountzinopoulou Fadel M. Garishah Cláudio Duarte-Oliveira Cláudia F. Campos Lore Vanderbeke Agustin Resendiz Sharpe Roger J. Brüggemann Paul E. Verweij Katrien Lagrou Greetje Vande Velde Quirijn de Mast Leo A.B. Joosten Mihai G. Netea Andre J.A.M. van der Ven Joost Wauters Agostinho Carvalho Frank L. van de Veerdonk |
author_sort |
Intan M.W. Dewi |
title |
Neuraminidase and SIGLEC15 modulate the host defense against pulmonary aspergillosis |
title_short |
Neuraminidase and SIGLEC15 modulate the host defense against pulmonary aspergillosis |
title_full |
Neuraminidase and SIGLEC15 modulate the host defense against pulmonary aspergillosis |
title_fullStr |
Neuraminidase and SIGLEC15 modulate the host defense against pulmonary aspergillosis |
title_full_unstemmed |
Neuraminidase and SIGLEC15 modulate the host defense against pulmonary aspergillosis |
title_sort |
neuraminidase and siglec15 modulate the host defense against pulmonary aspergillosis |
publisher |
Elsevier |
series |
Cell Reports Medicine |
issn |
2666-3791 |
publishDate |
2021-05-01 |
description |
Summary: Influenza-associated pulmonary aspergillosis (IAPA) has been reported increasingly since the advent of use of neuraminidase (NA) inhibitors following the 2009 influenza pandemic. We hypothesize that blocking host NA modulates the immune response against Aspergillus fumigatus. We demonstrate that NA influences the host response against A. fumigatus in vitro and that oseltamivir increases the susceptibility of mice to pulmonary aspergillosis. Oseltamivir impairs the mouse splenocyte and human peripheral blood mononuclear cell (PBMC) killing capacity of A. fumigatus, and adding NA restores this defect in PBMCs. Furthermore, the sialic acid-binding receptor SIGLEC15 is upregulated in PBMCs stimulated with A. fumigatus. Silencing of SIGLEC15 decrease PBMC killing of A. fumigatus. We provide evidence that host NA activity and sialic acid recognition are important for anti-Aspergillus defense. NA inhibitors might predispose individuals with severe influenza to invasive aspergillosis. These data shed light on the pathogenesis of invasive fungal infections and may identify potential therapeutic targets. |
topic |
aspergillosis neuraminidase oseltamivir SIGLEC15 |
url |
http://www.sciencedirect.com/science/article/pii/S2666379121001178 |
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doaj-6db0b061daa24bc6ab6079fafd1b44cf2021-05-20T07:53:15ZengElsevierCell Reports Medicine2666-37912021-05-0125100289Neuraminidase and SIGLEC15 modulate the host defense against pulmonary aspergillosisIntan M.W. Dewi0Cristina Cunha1Martin Jaeger2Mark S. Gresnigt3Marina E. Gkountzinopoulou4Fadel M. Garishah5Cláudio Duarte-Oliveira6Cláudia F. Campos7Lore Vanderbeke8Agustin Resendiz Sharpe9Roger J. Brüggemann10Paul E. Verweij11Katrien Lagrou12Greetje Vande Velde13Quirijn de Mast14Leo A.B. Joosten15Mihai G. Netea16Andre J.A.M. van der Ven17Joost Wauters18Agostinho Carvalho19Frank L. van de Veerdonk20Department of Internal Medicine, Radboud University Medical Center, Nijmegen, the Netherlands; Microbiology Division, Department of Biomedical Sciences, Faculty of Medicine, Universitas Padjadjaran, Bandung, IndonesiaLife and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Braga, Portugal; ICVS/3B’s – PT Government Associate Laboratory, Guimarães/Braga, PortugalDepartment of Internal Medicine, Radboud University Medical Center, Nijmegen, the NetherlandsDepartment of Microbial Pathogenicity Mechanisms, Leibniz Institute for Natural Product Research and Infection Biology-Hans Knoll Institute, Jena, GermanyDepartment of Internal Medicine, Radboud University Medical Center, Nijmegen, the NetherlandsDepartment of Internal Medicine, Radboud University Medical Center, Nijmegen, the NetherlandsLife and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Braga, Portugal; ICVS/3B’s – PT Government Associate Laboratory, Guimarães/Braga, PortugalLife and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Braga, Portugal; ICVS/3B’s – PT Government Associate Laboratory, Guimarães/Braga, PortugalDepartment of Microbiology and Immunology, KU Leuven, Leuven, BelgiumDepartment of Microbiology and Immunology, KU Leuven, Leuven, BelgiumDepartment of Pharmacy, Radboud University Medical Center, Nijmegen, the NetherlandsDepartment of Medical Microbiology, Radboud University Medical Centre, Nijmegen, the NetherlandsDepartment of Microbiology and Immunology, KU Leuven, Leuven, BelgiumBiomedical MRI/Molecular Small Animal Imaging Center, Department of Imaging and Pathology, KU Leuven, BelgiumDepartment of Internal Medicine, Radboud University Medical Center, Nijmegen, the NetherlandsDepartment of Internal Medicine, Radboud University Medical Center, Nijmegen, the NetherlandsDepartment of Internal Medicine, Radboud University Medical Center, Nijmegen, the NetherlandsDepartment of Internal Medicine, Radboud University Medical Center, Nijmegen, the NetherlandsDepartment of Microbiology and Immunology, KU Leuven, Leuven, BelgiumLife and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Braga, Portugal; ICVS/3B’s – PT Government Associate Laboratory, Guimarães/Braga, PortugalDepartment of Internal Medicine, Radboud University Medical Center, Nijmegen, the Netherlands; Corresponding authorSummary: Influenza-associated pulmonary aspergillosis (IAPA) has been reported increasingly since the advent of use of neuraminidase (NA) inhibitors following the 2009 influenza pandemic. We hypothesize that blocking host NA modulates the immune response against Aspergillus fumigatus. We demonstrate that NA influences the host response against A. fumigatus in vitro and that oseltamivir increases the susceptibility of mice to pulmonary aspergillosis. Oseltamivir impairs the mouse splenocyte and human peripheral blood mononuclear cell (PBMC) killing capacity of A. fumigatus, and adding NA restores this defect in PBMCs. Furthermore, the sialic acid-binding receptor SIGLEC15 is upregulated in PBMCs stimulated with A. fumigatus. Silencing of SIGLEC15 decrease PBMC killing of A. fumigatus. We provide evidence that host NA activity and sialic acid recognition are important for anti-Aspergillus defense. NA inhibitors might predispose individuals with severe influenza to invasive aspergillosis. These data shed light on the pathogenesis of invasive fungal infections and may identify potential therapeutic targets.http://www.sciencedirect.com/science/article/pii/S2666379121001178aspergillosisneuraminidaseoseltamivirSIGLEC15 |