A Human Dectin-2 Deficiency Associated with Invasive Aspergillosis

James S. Griffiths; P. Lewis White; Magdalena A. Czubala; Elena Simonazzi; Mariolina Bruno; Aiysha Thompson; Pierre J. Rizkallah; Mark Gurney; Diogo M. Da Fonseca; Julian R. Naglik; Wendy Ingram; Keith Wilson; Frank L. Van De Veerdonk; Rosemary Barnes; Philip R. Taylor; Selinda J. Orr

doi:10.1093/infdis/jiab145

A Human Dectin-2 Deficiency Associated with Invasive Aspergillosis

James S. Griffiths, P. Lewis White, Magdalena A. Czubala, Elena Simonazzi, Mariolina Bruno, Aiysha Thompson, Pierre J. Rizkallah, Mark Gurney, Diogo M. Da Fonseca, Julian R. Naglik, Wendy Ingram, Keith Wilson, Frank L. Van De Veerdonk, Rosemary Barnes, Philip R. Taylor, Selinda J. Orr^*

^*Corresponding author for this work

Centre for Host Microbiome Interactions

Research output: Contribution to journal › Article › peer-review

14 Citations (Scopus)

Abstract

Immunocompromised patients are highly susceptible to invasive aspergillosis. Herein, we identified a homozygous deletion mutation (507 del C) resulting in a frameshift (N170I) and early stop codon in the fungal binding Dectin-2 receptor, in an immunocompromised patient. The mutated form of Dectin-2 was weakly expressed, did not form clusters at/near the cell surface and was functionally defective. Peripheral blood mononuclear cells from this patient were unable to mount a cytokine (tumor necrosis factor, interleukin 6) response to Aspergillus fumigatus, and this first identified Dectin-2-deficient patient died of complications of invasive aspergillosis.

Original language	English
Pages (from-to)	1219-1224
Number of pages	6
Journal	Journal of Infectious Diseases
Volume	224
Issue number	7
DOIs	https://doi.org/10.1093/infdis/jiab145
Publication status	Published - 1 Oct 2021

Keywords

Aspergillus
Candida
CLR
Dectin-2
fungal immunology
host-pathogen interactions
inflammation
innate immunity

UN SDGs

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

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10.1093/infdis/jiab145

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Griffiths, J. S., White, P. L., Czubala, M. A., Simonazzi, E., Bruno, M., Thompson, A., Rizkallah, P. J., Gurney, M., Da Fonseca, D. M., Naglik, J. R., Ingram, W., Wilson, K., Van De Veerdonk, F. L., Barnes, R., Taylor, P. R., & Orr, S. J. (2021). A Human Dectin-2 Deficiency Associated with Invasive Aspergillosis. Journal of Infectious Diseases, 224(7), 1219-1224. https://doi.org/10.1093/infdis/jiab145

@article{f552f2e7ac744b10981a9c96b331f1a7,

title = "A Human Dectin-2 Deficiency Associated with Invasive Aspergillosis",

abstract = "Immunocompromised patients are highly susceptible to invasive aspergillosis. Herein, we identified a homozygous deletion mutation (507 del C) resulting in a frameshift (N170I) and early stop codon in the fungal binding Dectin-2 receptor, in an immunocompromised patient. The mutated form of Dectin-2 was weakly expressed, did not form clusters at/near the cell surface and was functionally defective. Peripheral blood mononuclear cells from this patient were unable to mount a cytokine (tumor necrosis factor, interleukin 6) response to Aspergillus fumigatus, and this first identified Dectin-2-deficient patient died of complications of invasive aspergillosis. ",

keywords = "Aspergillus, Candida, CLR, Dectin-2, fungal immunology, host-pathogen interactions, inflammation, innate immunity",

author = "Griffiths, {James S.} and White, {P. Lewis} and Czubala, {Magdalena A.} and Elena Simonazzi and Mariolina Bruno and Aiysha Thompson and Rizkallah, {Pierre J.} and Mark Gurney and {Da Fonseca}, {Diogo M.} and Naglik, {Julian R.} and Wendy Ingram and Keith Wilson and {Van De Veerdonk}, {Frank L.} and Rosemary Barnes and Taylor, {Philip R.} and Orr, {Selinda J.}",

note = "Funding Information: S. J. O. was funded by a Sir Henry Dale Fellowship jointly funded by the Wellcome Trust and the Royal Society (grant number 099953/Z/12/Z) and by the T. Maelgwyn Davies Bequest fund. P. R. T. is supported by a Wellcome Trust Investigator Award (107964/Z/15/Z) and the United Kingdom Dementia Research Institute. E. S. was supported by a Medical Research Council GW4 BioMed DTP PhD studentship. M. A. C. is supported by a Biotechnology and Biological Sciences Research Council Discovery Fellowship (BB/T009543/1). Publisher Copyright: {\textcopyright} 2021 The Author(s). Published by Oxford University Press for the Infectious Diseases Society of America.",

year = "2021",

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Griffiths, JS, White, PL, Czubala, MA, Simonazzi, E, Bruno, M, Thompson, A, Rizkallah, PJ, Gurney, M, Da Fonseca, DM, Naglik, JR, Ingram, W, Wilson, K, Van De Veerdonk, FL, Barnes, R, Taylor, PR & Orr, SJ 2021, 'A Human Dectin-2 Deficiency Associated with Invasive Aspergillosis', Journal of Infectious Diseases, vol. 224, no. 7, pp. 1219-1224. https://doi.org/10.1093/infdis/jiab145

TY - JOUR

T1 - A Human Dectin-2 Deficiency Associated with Invasive Aspergillosis

AU - Griffiths, James S.

AU - White, P. Lewis

AU - Czubala, Magdalena A.

AU - Simonazzi, Elena

AU - Bruno, Mariolina

AU - Thompson, Aiysha

AU - Rizkallah, Pierre J.

AU - Gurney, Mark

AU - Da Fonseca, Diogo M.

AU - Naglik, Julian R.

AU - Ingram, Wendy

AU - Wilson, Keith

AU - Van De Veerdonk, Frank L.

AU - Barnes, Rosemary

AU - Taylor, Philip R.

AU - Orr, Selinda J.

N1 - Funding Information: S. J. O. was funded by a Sir Henry Dale Fellowship jointly funded by the Wellcome Trust and the Royal Society (grant number 099953/Z/12/Z) and by the T. Maelgwyn Davies Bequest fund. P. R. T. is supported by a Wellcome Trust Investigator Award (107964/Z/15/Z) and the United Kingdom Dementia Research Institute. E. S. was supported by a Medical Research Council GW4 BioMed DTP PhD studentship. M. A. C. is supported by a Biotechnology and Biological Sciences Research Council Discovery Fellowship (BB/T009543/1). Publisher Copyright: © 2021 The Author(s). Published by Oxford University Press for the Infectious Diseases Society of America.

PY - 2021/10/1

Y1 - 2021/10/1

N2 - Immunocompromised patients are highly susceptible to invasive aspergillosis. Herein, we identified a homozygous deletion mutation (507 del C) resulting in a frameshift (N170I) and early stop codon in the fungal binding Dectin-2 receptor, in an immunocompromised patient. The mutated form of Dectin-2 was weakly expressed, did not form clusters at/near the cell surface and was functionally defective. Peripheral blood mononuclear cells from this patient were unable to mount a cytokine (tumor necrosis factor, interleukin 6) response to Aspergillus fumigatus, and this first identified Dectin-2-deficient patient died of complications of invasive aspergillosis.

AB - Immunocompromised patients are highly susceptible to invasive aspergillosis. Herein, we identified a homozygous deletion mutation (507 del C) resulting in a frameshift (N170I) and early stop codon in the fungal binding Dectin-2 receptor, in an immunocompromised patient. The mutated form of Dectin-2 was weakly expressed, did not form clusters at/near the cell surface and was functionally defective. Peripheral blood mononuclear cells from this patient were unable to mount a cytokine (tumor necrosis factor, interleukin 6) response to Aspergillus fumigatus, and this first identified Dectin-2-deficient patient died of complications of invasive aspergillosis.

KW - Aspergillus

KW - Candida

KW - CLR

KW - Dectin-2

KW - fungal immunology

KW - host-pathogen interactions

KW - inflammation

KW - innate immunity

UR - http://www.scopus.com/inward/record.url?scp=85118904337&partnerID=8YFLogxK

U2 - 10.1093/infdis/jiab145

DO - 10.1093/infdis/jiab145

M3 - Article

C2 - 33733279

AN - SCOPUS:85118904337

SN - 0022-1899

VL - 224

SP - 1219

EP - 1224

JO - Journal of Infectious Diseases

JF - Journal of Infectious Diseases

IS - 7

ER -

A Human Dectin-2 Deficiency Associated with Invasive Aspergillosis

Abstract

Keywords

UN SDGs

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