Neuraminidase and SIGLEC15 modulate the host defense against pulmonary aspergillosis

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

doi:10.1016/j.xcrm.2021.100289

Neuraminidase and SIGLEC15 modulate the host defense against pulmonary aspergillosis

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 CarvalhoFrank L. van de Veerdonk

Onderzoeksoutput: Bijdrage aan tijdschrift › Artikel › peer review

22 Citaten (Scopus)

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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.

Originele taal-2	Engels
Artikelnummer	100289
Tijdschrift	Cell Reports Medicine
Volume	2
Nummer van het tijdschrift	5
DOI's	https://doi.org/10.1016/j.xcrm.2021.100289
Status	Gepubliceerd - 18 mei 2021
Extern gepubliceerd	Ja

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Dewi, I. M. W., Cunha, C., Jaeger, M., Gresnigt, M. S., Gkountzinopoulou, M. E., Garishah, F. M., Duarte-Oliveira, C., Campos, C. F., Vanderbeke, L., Sharpe, A. R., Brüggemann, R. J., Verweij, P. E., Lagrou, K., Vande Velde, G., de Mast, Q., Joosten, L. A. B., Netea, M. G., van der Ven, A. J. A. M., Wauters, J., ... van de Veerdonk, F. L. (2021). Neuraminidase and SIGLEC15 modulate the host defense against pulmonary aspergillosis. Cell Reports Medicine, 2(5), Artikel 100289. https://doi.org/10.1016/j.xcrm.2021.100289

@article{36add75b663941b4aeebd4b8d5a7b938,

title = "Neuraminidase and SIGLEC15 modulate the host defense against pulmonary aspergillosis",

abstract = "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.",

keywords = "aspergillosis, neuraminidase, oseltamivir, SIGLEC15",

author = "Dewi, {Intan M.W.} and Cristina Cunha and Martin Jaeger and Gresnigt, {Mark S.} and Gkountzinopoulou, {Marina E.} and Garishah, {Fadel M.} and Cl{\'a}udio Duarte-Oliveira and Campos, {Cl{\'a}udia F.} and Lore Vanderbeke and Sharpe, {Agustin Resendiz} and Br{\"u}ggemann, {Roger J.} and Verweij, {Paul E.} and Katrien Lagrou and {Vande Velde}, Greetje and {de Mast}, Quirijn and Joosten, {Leo A.B.} and Netea, {Mihai G.} and {van der Ven}, {Andre J.A.M.} and Joost Wauters and Agostinho Carvalho and {van de Veerdonk}, {Frank L.}",

note = "Publisher Copyright: {\textcopyright} 2021 The Authors",

year = "2021",

month = may,

day = "18",

doi = "10.1016/j.xcrm.2021.100289",

language = "English",

volume = "2",

journal = "Cell Reports Medicine",

issn = "2666-3791",

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Dewi, IMW, Cunha, C, Jaeger, M, Gresnigt, MS, Gkountzinopoulou, ME, Garishah, FM, Duarte-Oliveira, C, Campos, CF, Vanderbeke, L, Sharpe, AR, Brüggemann, RJ, Verweij, PE, Lagrou, K, Vande Velde, G, de Mast, Q, Joosten, LAB, Netea, MG, van der Ven, AJAM, Wauters, J, Carvalho, A & van de Veerdonk, FL 2021, 'Neuraminidase and SIGLEC15 modulate the host defense against pulmonary aspergillosis', Cell Reports Medicine, vol. 2, nr. 5, 100289. https://doi.org/10.1016/j.xcrm.2021.100289

TY - JOUR

T1 - Neuraminidase and SIGLEC15 modulate the host defense against pulmonary aspergillosis

AU - Dewi, Intan M.W.

AU - Cunha, Cristina

AU - Jaeger, Martin

AU - Gresnigt, Mark S.

AU - Gkountzinopoulou, Marina E.

AU - Garishah, Fadel M.

AU - Duarte-Oliveira, Cláudio

AU - Campos, Cláudia F.

AU - Vanderbeke, Lore

AU - Sharpe, Agustin Resendiz

AU - Brüggemann, Roger J.

AU - Verweij, Paul E.

AU - Lagrou, Katrien

AU - Vande Velde, Greetje

AU - de Mast, Quirijn

AU - Joosten, Leo A.B.

AU - Netea, Mihai G.

AU - van der Ven, Andre J.A.M.

AU - Wauters, Joost

AU - Carvalho, Agostinho

AU - van de Veerdonk, Frank L.

PY - 2021/5/18

Y1 - 2021/5/18

N2 - 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.

AB - 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.

KW - aspergillosis

KW - neuraminidase

KW - oseltamivir

KW - SIGLEC15

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U2 - 10.1016/j.xcrm.2021.100289

DO - 10.1016/j.xcrm.2021.100289

M3 - Article

C2 - 34095887

AN - SCOPUS:85106328125

SN - 2666-3791

VL - 2

JO - Cell Reports Medicine

JF - Cell Reports Medicine

IS - 5

M1 - 100289

ER -

Neuraminidase and SIGLEC15 modulate the host defense against pulmonary aspergillosis

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