Differential Adaptation of Candida albicans In Vivo Modulates Immune Recognition by Dectin-1

Mohlopheni J. Marakalala; Simon Vautier; Joanna Potrykus; Louise A. Walker; Kelly M. Shepardson; Alex Hopke; Hector M. Mora-Montes; Keunsook K.  Lee; Ann Kerrigan; Mihai G. Netea; Graeme I. Murray; Donna M. MacCallum; Robert Wheeler; Carol A. Munro; Neil A.R. Gow; Robert A. Cramer; Alistair J.P. Brown; Gordon D. Brown

doi:10.1371/journal.ppat.1003315

Differential Adaptation of Candida albicans In Vivo Modulates Immune Recognition by Dectin-1

Mohlopheni J. Marakalala, Simon Vautier, Joanna Potrykus, Louise A. Walker, Kelly M. Shepardson, Alex Hopke, Hector M. Mora-Montes, Keunsook K. Lee , Ann Kerrigan, Mihai G. Netea, Graeme I. Murray, Donna M. MacCallum, Robert Wheeler, Carol A. Munro, Neil A.R. Gow, Robert A. Cramer, Alistair J.P. Brown, Gordon D. Brown

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Abstract

The β-glucan receptor Dectin-1 is a member of the C-type lectin family and functions as an innate pattern recognition receptor in antifungal immunity. In both mouse and man, Dectin-1 has been found to play an essential role in controlling infections with Candida albicans, a normally commensal fungus in man which can cause superficial mucocutaneous infections as well as life-threatening invasive diseases. Here, using in vivo models of infection, we show that the requirement for Dectin-1 in the control of systemic Candida albicans infections is fungal strain-specific; a phenotype that only becomes apparent during infection and cannot be recapitulated in vitro. Transcript analysis revealed that this differential requirement for Dectin-1 is due to variable adaptation of C. albicans strains in vivo, and that this results in substantial differences in the composition and nature of their cell walls. In particular, we established that differences in the levels of cell-wall chitin influence the role of Dectin-1, and that these effects can be modulated by antifungal drug treatment. Our results therefore provide substantial new insights into the interaction between C. albicans and the immune system and have significant implications for our understanding of susceptibility and treatment of human infections with this pathogen.

Original language	English
Article number	e1003315
Number of pages	12
Journal	PLoS Pathogens
Volume	9
Issue number	4
DOIs	https://doi.org/10.1371/journal.ppat.1003315
Publication status	Published - 18 Apr 2013
Externally published	Yes

Bibliographical note

Copyright: © 2013 Marakalala et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Copyright © and Moral Rights are retained by the author(s) and/ or other copyright owners. A copy can be downloaded for personal non-commercial research or study, without prior permission or charge. This item cannot be reproduced or quoted extensively from without first obtaining permission in writing from the copyright holder(s). The content must not be changed in any way or sold commercially in any format or medium without the formal permission of the copyright holders.

ASJC Scopus subject areas

Parasitology
Microbiology
Immunology
Molecular Biology
Genetics
Virology

UN SDGs

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

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10.1371/journal.ppat.1003315Licence: CC BY

PublishedFinal published version, 2.47 MBLicence: CC BY

Cite this

Marakalala, M. J., Vautier, S., Potrykus, J., Walker, L. A., Shepardson, K. M., Hopke, A., Mora-Montes, H. M., Lee , K. K., Kerrigan, A., Netea, M. G., Murray, G. I., MacCallum, D. M., Wheeler, R., Munro, C. A., Gow, N. A. R., Cramer, R. A., Brown, A. J. P., & Brown, G. D. (2013). Differential Adaptation of Candida albicans In Vivo Modulates Immune Recognition by Dectin-1. PLoS Pathogens, 9(4), [e1003315]. https://doi.org/10.1371/journal.ppat.1003315

Marakalala, MJ, Vautier, S, Potrykus, J, Walker, LA, Shepardson, KM, Hopke, A, Mora-Montes, HM, Lee , KK, Kerrigan, A, Netea, MG, Murray, GI, MacCallum, DM, Wheeler, R, Munro, CA, Gow, NAR, Cramer, RA, Brown, AJP & Brown, GD 2013, 'Differential Adaptation of Candida albicans In Vivo Modulates Immune Recognition by Dectin-1', PLoS Pathogens, vol. 9, no. 4, e1003315. https://doi.org/10.1371/journal.ppat.1003315

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abstract = "The β-glucan receptor Dectin-1 is a member of the C-type lectin family and functions as an innate pattern recognition receptor in antifungal immunity. In both mouse and man, Dectin-1 has been found to play an essential role in controlling infections with Candida albicans, a normally commensal fungus in man which can cause superficial mucocutaneous infections as well as life-threatening invasive diseases. Here, using in vivo models of infection, we show that the requirement for Dectin-1 in the control of systemic Candida albicans infections is fungal strain-specific; a phenotype that only becomes apparent during infection and cannot be recapitulated in vitro. Transcript analysis revealed that this differential requirement for Dectin-1 is due to variable adaptation of C. albicans strains in vivo, and that this results in substantial differences in the composition and nature of their cell walls. In particular, we established that differences in the levels of cell-wall chitin influence the role of Dectin-1, and that these effects can be modulated by antifungal drug treatment. Our results therefore provide substantial new insights into the interaction between C. albicans and the immune system and have significant implications for our understanding of susceptibility and treatment of human infections with this pathogen.",

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AU - Walker, Louise A.

AU - Shepardson, Kelly M.

AU - Hopke, Alex

AU - Mora-Montes, Hector M.

AU - Lee , Keunsook K.

AU - Kerrigan, Ann

AU - Netea, Mihai G.

AU - Murray, Graeme I.

AU - MacCallum, Donna M.

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AU - Munro, Carol A.

AU - Gow, Neil A.R.

AU - Cramer, Robert A.

AU - Brown, Alistair J.P.

AU - Brown, Gordon D.

N1 - Copyright: © 2013 Marakalala et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Copyright © and Moral Rights are retained by the author(s) and/ or other copyright owners. A copy can be downloaded for personal non-commercial research or study, without prior permission or charge. This item cannot be reproduced or quoted extensively from without first obtaining permission in writing from the copyright holder(s). The content must not be changed in any way or sold commercially in any format or medium without the formal permission of the copyright holders.

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N2 - The β-glucan receptor Dectin-1 is a member of the C-type lectin family and functions as an innate pattern recognition receptor in antifungal immunity. In both mouse and man, Dectin-1 has been found to play an essential role in controlling infections with Candida albicans, a normally commensal fungus in man which can cause superficial mucocutaneous infections as well as life-threatening invasive diseases. Here, using in vivo models of infection, we show that the requirement for Dectin-1 in the control of systemic Candida albicans infections is fungal strain-specific; a phenotype that only becomes apparent during infection and cannot be recapitulated in vitro. Transcript analysis revealed that this differential requirement for Dectin-1 is due to variable adaptation of C. albicans strains in vivo, and that this results in substantial differences in the composition and nature of their cell walls. In particular, we established that differences in the levels of cell-wall chitin influence the role of Dectin-1, and that these effects can be modulated by antifungal drug treatment. Our results therefore provide substantial new insights into the interaction between C. albicans and the immune system and have significant implications for our understanding of susceptibility and treatment of human infections with this pathogen.

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Differential Adaptation of Candida albicans In Vivo Modulates Immune Recognition by Dectin-1

Abstract

Bibliographical note

ASJC Scopus subject areas

UN SDGs

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