Lactate signalling regulates fungal β-glucan masking and immune evasion

Elizabeth Ballou; Gabriela M. Avelar; Delma S. Childers; Joanna Mackie; Judith M. Bain; Jeanette Wagener; Stavroula  L. Kastora; M. D. Panea; Sarah E. Hardison; Louise Walker; Lars P. Erwig; Carol A. Munro; Neil A. R. Gow; G. D. Brown; Donna M. MacCallum; Alistair J. P. Brown

doi:10.1038/nmicrobiol.2016.238

Lactate signalling regulates fungal β-glucan masking and immune evasion

Elizabeth Ballou, Gabriela M. Avelar, Delma S. Childers, Joanna Mackie, Judith M. Bain, Jeanette Wagener, Stavroula L. Kastora, M. D. Panea, Sarah E. Hardison, Louise Walker, Lars P. Erwig, Carol A. Munro, Neil A. R. Gow, G. D. Brown, Donna M. MacCallum, Alistair J. P. Brown^* (Corresponding Author)

^*Corresponding author for this work

University of Aberdeen

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

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Abstract

As they proliferate, fungi expose antigens at their cell surface that are potent stimulators of the innate immune response, and yet the commensal fungus Candida albicans is able to colonize immuno competent individuals. We show that C. albicans may evade immune detection by presenting a moving immunological target. We report that the exposure of β-glucan, a key pathogen-associated molecular pattern (PAMP) located at the cell surface of C. albicans and other pathogenic Candida species, is modulated in response to changes in the carbon source. Exposure to lactate induces β-glucan masking in C. albicans via a signalling pathway that has recruited an evolutionarily conserved receptor (Gpr1) and transcriptional factor (Crz1) from other well-characterized pathways. In response to lactate, these regulators control the expression of cell-wall-related genes that contribute to β-glucan masking. This represents the first description of active PAMP masking by a Candida species, a process that reduces the visibility of the fungus to the immune system.

Original language	English
Article number	16238
Journal	Nature Microbiology
Volume	2
DOIs	https://doi.org/10.1038/nmicrobiol.2016.238
Publication status	Published - 12 Dec 2016

Bibliographical note

AJPB: This work was supported by the European Research Council (STRIFE, ERC-
2009-AdG-249793), The UK Medical Research Council (MR/M026663/1), the UK Biotechnology and Biological Research Council (BB/K017365/1), the Wellcome Trust (080088; 097377). ERB: This work was supported by the UK Biotechnology and Biological Research Council (BB/M014525/1). GMA: Supported by the CNPq-Brazil (Science without Borders fellowship 202976/2014-9). GDB: Wellcome Trust (102705). CAM: This work was supported by the UK Medical Research Council (G0400284). DMM: This work was supported by UK National Centre for the Replacement, Refinement and Reduction of Animals in Research (NC/K000306/1). NARG/JW: Wellcome Trust (086827, 075470,101873) and Wellcome Trust Strategic Award in Medical Mycology and Fungal Immunology (097377). ALL: This work was supported by the MRC Centre for Medical Mycology and the University of Aberdeen (MR/N006364/1).

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Delma Childers
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Donna MacCallum
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Carol Munro
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Ballou, E., M. Avelar, G., Childers, D. S., Mackie, J., Bain, J. M., Wagener, J., Kastora, S. L., Panea, M. D., Hardison, S. E., Walker, L., Erwig, L. P., Munro, C. A., Gow, N. A. R., Brown, G. D., MacCallum, D. M., & Brown, A. J. P. (2016). Lactate signalling regulates fungal β-glucan masking and immune evasion. Nature Microbiology, 2, Article 16238. https://doi.org/10.1038/nmicrobiol.2016.238

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title = "Lactate signalling regulates fungal β-glucan masking and immune evasion",

abstract = "As they proliferate, fungi expose antigens at their cell surface that are potent stimulators of the innate immune response, and yet the commensal fungus Candida albicans is able to colonize immuno competent individuals. We show that C. albicans may evade immune detection by presenting a moving immunological target. We report that the exposure of β-glucan, a key pathogen-associated molecular pattern (PAMP) located at the cell surface of C. albicans and other pathogenic Candida species, is modulated in response to changes in the carbon source. Exposure to lactate induces β-glucan masking in C. albicans via a signalling pathway that has recruited an evolutionarily conserved receptor (Gpr1) and transcriptional factor (Crz1) from other well-characterized pathways. In response to lactate, these regulators control the expression of cell-wall-related genes that contribute to β-glucan masking. This represents the first description of active PAMP masking by a Candida species, a process that reduces the visibility of the fungus to the immune system.",

author = "Elizabeth Ballou and {M. Avelar}, Gabriela and Childers, {Delma S.} and Joanna Mackie and Bain, {Judith M.} and Jeanette Wagener and Kastora, {Stavroula L.} and Panea, {M. D.} and Hardison, {Sarah E.} and Louise Walker and Erwig, {Lars P.} and Munro, {Carol A.} and Gow, {Neil A. R.} and Brown, {G. D.} and MacCallum, {Donna M.} and Brown, {Alistair J. P.}",

note = "AJPB: This work was supported by the European Research Council (STRIFE, ERC- 2009-AdG-249793), The UK Medical Research Council (MR/M026663/1), the UK Biotechnology and Biological Research Council (BB/K017365/1), the Wellcome Trust (080088; 097377). ERB: This work was supported by the UK Biotechnology and Biological Research Council (BB/M014525/1). GMA: Supported by the CNPq-Brazil (Science without Borders fellowship 202976/2014-9). GDB: Wellcome Trust (102705). CAM: This work was supported by the UK Medical Research Council (G0400284). DMM: This work was supported by UK National Centre for the Replacement, Refinement and Reduction of Animals in Research (NC/K000306/1). NARG/JW: Wellcome Trust (086827, 075470,101873) and Wellcome Trust Strategic Award in Medical Mycology and Fungal Immunology (097377). ALL: This work was supported by the MRC Centre for Medical Mycology and the University of Aberdeen (MR/N006364/1).",

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AU - M. Avelar, Gabriela

AU - Childers, Delma S.

AU - Mackie, Joanna

AU - Bain, Judith M.

AU - Wagener, Jeanette

AU - Kastora, Stavroula L.

AU - Panea, M. D.

AU - Hardison, Sarah E.

AU - Walker, Louise

AU - Erwig, Lars P.

AU - Munro, Carol A.

AU - Gow, Neil A. R.

AU - Brown, G. D.

AU - MacCallum, Donna M.

AU - Brown, Alistair J. P.

N1 - AJPB: This work was supported by the European Research Council (STRIFE, ERC- 2009-AdG-249793), The UK Medical Research Council (MR/M026663/1), the UK Biotechnology and Biological Research Council (BB/K017365/1), the Wellcome Trust (080088; 097377). ERB: This work was supported by the UK Biotechnology and Biological Research Council (BB/M014525/1). GMA: Supported by the CNPq-Brazil (Science without Borders fellowship 202976/2014-9). GDB: Wellcome Trust (102705). CAM: This work was supported by the UK Medical Research Council (G0400284). DMM: This work was supported by UK National Centre for the Replacement, Refinement and Reduction of Animals in Research (NC/K000306/1). NARG/JW: Wellcome Trust (086827, 075470,101873) and Wellcome Trust Strategic Award in Medical Mycology and Fungal Immunology (097377). ALL: This work was supported by the MRC Centre for Medical Mycology and the University of Aberdeen (MR/N006364/1).

PY - 2016/12/12

Y1 - 2016/12/12

N2 - As they proliferate, fungi expose antigens at their cell surface that are potent stimulators of the innate immune response, and yet the commensal fungus Candida albicans is able to colonize immuno competent individuals. We show that C. albicans may evade immune detection by presenting a moving immunological target. We report that the exposure of β-glucan, a key pathogen-associated molecular pattern (PAMP) located at the cell surface of C. albicans and other pathogenic Candida species, is modulated in response to changes in the carbon source. Exposure to lactate induces β-glucan masking in C. albicans via a signalling pathway that has recruited an evolutionarily conserved receptor (Gpr1) and transcriptional factor (Crz1) from other well-characterized pathways. In response to lactate, these regulators control the expression of cell-wall-related genes that contribute to β-glucan masking. This represents the first description of active PAMP masking by a Candida species, a process that reduces the visibility of the fungus to the immune system.

AB - As they proliferate, fungi expose antigens at their cell surface that are potent stimulators of the innate immune response, and yet the commensal fungus Candida albicans is able to colonize immuno competent individuals. We show that C. albicans may evade immune detection by presenting a moving immunological target. We report that the exposure of β-glucan, a key pathogen-associated molecular pattern (PAMP) located at the cell surface of C. albicans and other pathogenic Candida species, is modulated in response to changes in the carbon source. Exposure to lactate induces β-glucan masking in C. albicans via a signalling pathway that has recruited an evolutionarily conserved receptor (Gpr1) and transcriptional factor (Crz1) from other well-characterized pathways. In response to lactate, these regulators control the expression of cell-wall-related genes that contribute to β-glucan masking. This represents the first description of active PAMP masking by a Candida species, a process that reduces the visibility of the fungus to the immune system.

U2 - 10.1038/nmicrobiol.2016.238

DO - 10.1038/nmicrobiol.2016.238

M3 - Article

SN - 2058-5276

VL - 2

JO - Nature Microbiology

JF - Nature Microbiology

M1 - 16238

ER -

Lactate signalling regulates fungal β-glucan masking and immune evasion

Abstract

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