Transcriptional and functional insights into the host immune response against the emerging fungal pathogen Candida auris

Mariolina Bruno; Simone  Kersten; Judith M. Bain; Martin Jaeger; Diletta  Rosati; Michael D Kruppa; Douglas W. Lowman; Peter J.  Rice; Bridget Graves; Ma  Zuchao; Y.  Ning Jiao; Anuradha Chowdhary; George  Renieris; Frank L van de Veerdonk; Bart-Jan Kullberg; Evangelos J.  Giamarellos-Bourboulis; Alexander Hoischen; Neil A.R. Gow; Alistair J.P.  Brown; Jacques F. Meis; David L Williams; Mihai G. Netea

doi:10.1038/s41564-020-0780-3

Transcriptional and functional insights into the host immune response against the emerging fungal pathogen Candida auris

Mariolina Bruno^* (Corresponding Author), Simone Kersten, Judith M. Bain, Martin Jaeger, Diletta Rosati, Michael D Kruppa, Douglas W. Lowman, Peter J. Rice, Bridget Graves, Ma Zuchao, Y. Ning Jiao, Anuradha Chowdhary, George Renieris, Frank L van de Veerdonk, Bart-Jan Kullberg, Evangelos J. Giamarellos-Bourboulis, Alexander Hoischen, Neil A.R. Gow, Alistair J.P. Brown, Jacques F. MeisDavid L Williams, Mihai G. Netea^* (Corresponding Author)

^*Corresponding author for this work

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Abstract

Candida auris is among the most important emerging fungal pathogens, yet mechanistic insights into its immune recognition and control are lacking. Here, we integrate transcriptional and functional immune-cell profiling to uncover innate defence mechanisms against C. auris. C. auris induces a specific transcriptome in human mononuclear cells, a stronger cytokine response compared with Candida albicans, but a lower macrophage lysis capacity. C. auris-induced innate immune activation is mediated through the recognition of C-type lectin receptors, mainly elicited by structurally unique C. auris mannoproteins. In in vivo experimental models of disseminated candidiasis, C. auris was less virulent than C. albicans. Collectively, these results demonstrate that C. auris is a strong inducer of innate host defence, and identify possible targets for adjuvant immunotherapy.

Original language	English
Pages (from-to)	1516-1531
Number of pages	16
Journal	Nature Microbiology
Volume	5
Early online date	24 Aug 2020
DOIs	https://doi.org/10.1038/s41564-020-0780-3
Publication status	Published - Dec 2020

Bibliographical note

ACKNOWLEDGMENTS:
We would like to thank Trees Jansen for performing the initial pilot experiments and Ilse Curfs-Breuker and Dirk Faro for their support at the CWZ hospital. We thank Charlotte Kaffa, BSc. for her technical assistance. We would like to thank Vinod Kumar for his input during the transcriptomic data analysis, Mark Gresnigt for the in vitro experimental suggestions and Anouk Becker for the help during the revision experiments. AJPB and NARG thank the MRC (MR/M026663/1) and Wellcome for support and the Medical Research Council (MRC) Centre for Medical Mycology at the University of Aberdeen (MR/N006364/1). A.H. and S.K. were supported by the Radboud Institute for Molecular Life Sciences. Part of the study was supported by the Hellenic Institute for the Study of Sepsis. D.L.W. was supported by National Institutes of Health grants NIH GM083016, GM119197 and C06RR0306551. M.G.N. was supported by an ERC Advanced Grant (no. 833247) and a Spinoza Grant from the Netherlands Organization for Scientific Research.

Keywords

fungal host response
fungal infection
YEAST
SURVIVAL
LECTIN
RECOGNITION
ALBICANS
MANNAN
RESISTANT CANDIDA-AURIS
EMERGENCE
GLUCAN

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This is a post-peer-review, pre-copyedit version of an article published in Nature Microbiology. The final authenticated version is available online at: https://doi.org/10.1038/s41564-020-0780-3
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Bruno, M., Kersten, S., Bain, J. M., Jaeger, M., Rosati, D., Kruppa, M. D., Lowman, D. W., Rice, P. J., Graves, B., Zuchao, M., Ning Jiao, Y., Chowdhary, A., Renieris, G., van de Veerdonk, F. L., Kullberg, B.-J., Giamarellos-Bourboulis, E. J., Hoischen, A., Gow, N. A. R., Brown, A. J. P., ... Netea, M. G. (2020). Transcriptional and functional insights into the host immune response against the emerging fungal pathogen Candida auris. Nature Microbiology, 5, 1516-1531. https://doi.org/10.1038/s41564-020-0780-3

Bruno, M, Kersten, S, Bain, JM, Jaeger, M, Rosati, D, Kruppa, MD, Lowman, DW, Rice, PJ, Graves, B, Zuchao, M, Ning Jiao, Y, Chowdhary, A, Renieris, G, van de Veerdonk, FL, Kullberg, B-J, Giamarellos-Bourboulis, EJ, Hoischen, A, Gow, NAR, Brown, AJP, Meis, JF, Williams, DL & Netea, MG 2020, 'Transcriptional and functional insights into the host immune response against the emerging fungal pathogen Candida auris', Nature Microbiology, vol. 5, pp. 1516-1531. https://doi.org/10.1038/s41564-020-0780-3

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title = "Transcriptional and functional insights into the host immune response against the emerging fungal pathogen Candida auris",

abstract = "Candida auris is among the most important emerging fungal pathogens, yet mechanistic insights into its immune recognition and control are lacking. Here, we integrate transcriptional and functional immune-cell profiling to uncover innate defence mechanisms against C. auris. C. auris induces a specific transcriptome in human mononuclear cells, a stronger cytokine response compared with Candida albicans, but a lower macrophage lysis capacity. C. auris-induced innate immune activation is mediated through the recognition of C-type lectin receptors, mainly elicited by structurally unique C. auris mannoproteins. In in vivo experimental models of disseminated candidiasis, C. auris was less virulent than C. albicans. Collectively, these results demonstrate that C. auris is a strong inducer of innate host defence, and identify possible targets for adjuvant immunotherapy.",

keywords = "fungal host response, fungal infection, YEAST, SURVIVAL, LECTIN, RECOGNITION, ALBICANS, MANNAN, RESISTANT CANDIDA-AURIS, EMERGENCE, GLUCAN",

author = "Mariolina Bruno and Simone Kersten and Bain, {Judith M.} and Martin Jaeger and Diletta Rosati and Kruppa, {Michael D} and Lowman, {Douglas W.} and Rice, {Peter J.} and Bridget Graves and Ma Zuchao and {Ning Jiao}, Y. and Anuradha Chowdhary and George Renieris and {van de Veerdonk}, {Frank L} and Bart-Jan Kullberg and Giamarellos-Bourboulis, {Evangelos J.} and Alexander Hoischen and Gow, {Neil A.R.} and Brown, {Alistair J.P.} and Meis, {Jacques F.} and Williams, {David L} and Netea, {Mihai G.}",

note = "ACKNOWLEDGMENTS: We would like to thank Trees Jansen for performing the initial pilot experiments and Ilse Curfs-Breuker and Dirk Faro for their support at the CWZ hospital. We thank Charlotte Kaffa, BSc. for her technical assistance. We would like to thank Vinod Kumar for his input during the transcriptomic data analysis, Mark Gresnigt for the in vitro experimental suggestions and Anouk Becker for the help during the revision experiments. AJPB and NARG thank the MRC (MR/M026663/1) and Wellcome for support and the Medical Research Council (MRC) Centre for Medical Mycology at the University of Aberdeen (MR/N006364/1). A.H. and S.K. were supported by the Radboud Institute for Molecular Life Sciences. Part of the study was supported by the Hellenic Institute for the Study of Sepsis. D.L.W. was supported by National Institutes of Health grants NIH GM083016, GM119197 and C06RR0306551. M.G.N. was supported by an ERC Advanced Grant (no. 833247) and a Spinoza Grant from the Netherlands Organization for Scientific Research. ",

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doi = "10.1038/s41564-020-0780-3",

language = "English",

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journal = "Nature Microbiology",

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T1 - Transcriptional and functional insights into the host immune response against the emerging fungal pathogen Candida auris

AU - Bruno, Mariolina

AU - Kersten, Simone

AU - Bain, Judith M.

AU - Jaeger, Martin

AU - Rosati, Diletta

AU - Kruppa, Michael D

AU - Lowman, Douglas W.

AU - Rice, Peter J.

AU - Graves, Bridget

AU - Zuchao, Ma

AU - Ning Jiao, Y.

AU - Chowdhary, Anuradha

AU - Renieris, George

AU - van de Veerdonk, Frank L

AU - Kullberg, Bart-Jan

AU - Giamarellos-Bourboulis, Evangelos J.

AU - Hoischen, Alexander

AU - Gow, Neil A.R.

AU - Brown, Alistair J.P.

AU - Meis, Jacques F.

AU - Williams, David L

AU - Netea, Mihai G.

N1 - ACKNOWLEDGMENTS: We would like to thank Trees Jansen for performing the initial pilot experiments and Ilse Curfs-Breuker and Dirk Faro for their support at the CWZ hospital. We thank Charlotte Kaffa, BSc. for her technical assistance. We would like to thank Vinod Kumar for his input during the transcriptomic data analysis, Mark Gresnigt for the in vitro experimental suggestions and Anouk Becker for the help during the revision experiments. AJPB and NARG thank the MRC (MR/M026663/1) and Wellcome for support and the Medical Research Council (MRC) Centre for Medical Mycology at the University of Aberdeen (MR/N006364/1). A.H. and S.K. were supported by the Radboud Institute for Molecular Life Sciences. Part of the study was supported by the Hellenic Institute for the Study of Sepsis. D.L.W. was supported by National Institutes of Health grants NIH GM083016, GM119197 and C06RR0306551. M.G.N. was supported by an ERC Advanced Grant (no. 833247) and a Spinoza Grant from the Netherlands Organization for Scientific Research.

PY - 2020/12

Y1 - 2020/12

N2 - Candida auris is among the most important emerging fungal pathogens, yet mechanistic insights into its immune recognition and control are lacking. Here, we integrate transcriptional and functional immune-cell profiling to uncover innate defence mechanisms against C. auris. C. auris induces a specific transcriptome in human mononuclear cells, a stronger cytokine response compared with Candida albicans, but a lower macrophage lysis capacity. C. auris-induced innate immune activation is mediated through the recognition of C-type lectin receptors, mainly elicited by structurally unique C. auris mannoproteins. In in vivo experimental models of disseminated candidiasis, C. auris was less virulent than C. albicans. Collectively, these results demonstrate that C. auris is a strong inducer of innate host defence, and identify possible targets for adjuvant immunotherapy.

AB - Candida auris is among the most important emerging fungal pathogens, yet mechanistic insights into its immune recognition and control are lacking. Here, we integrate transcriptional and functional immune-cell profiling to uncover innate defence mechanisms against C. auris. C. auris induces a specific transcriptome in human mononuclear cells, a stronger cytokine response compared with Candida albicans, but a lower macrophage lysis capacity. C. auris-induced innate immune activation is mediated through the recognition of C-type lectin receptors, mainly elicited by structurally unique C. auris mannoproteins. In in vivo experimental models of disseminated candidiasis, C. auris was less virulent than C. albicans. Collectively, these results demonstrate that C. auris is a strong inducer of innate host defence, and identify possible targets for adjuvant immunotherapy.

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KW - fungal infection

KW - YEAST

KW - SURVIVAL

KW - LECTIN

KW - RECOGNITION

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KW - MANNAN

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KW - EMERGENCE

KW - GLUCAN

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U2 - 10.1038/s41564-020-0780-3

DO - 10.1038/s41564-020-0780-3

M3 - Article

C2 - 32839538

SN - 2058-5276

VL - 5

SP - 1516

EP - 1531

JO - Nature Microbiology

JF - Nature Microbiology

ER -

Transcriptional and functional insights into the host immune response against the emerging fungal pathogen Candida auris

Abstract

Bibliographical note

Keywords

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