Adaptation of Candida albicans to environmental pH induces cell wall remodelling and enhances innate immune recognition

Sarah L. Sherrington; Eleanor Sorsby; Nabeel  Mahtey; Pizga Kumwenda; Megan Lenardon; Ian Brown; Elizabeth Ballou; Donna M MacCallum; Rebecca A.  Hall

doi:10.1371/journal.ppat.1006403

Adaptation of Candida albicans to environmental pH induces cell wall remodelling and enhances innate immune recognition

Sarah L. Sherrington, Eleanor Sorsby, Nabeel Mahtey, Pizga Kumwenda, Megan Lenardon, Ian Brown, Elizabeth Ballou, Donna M MacCallum, Rebecca A. Hall

Medical Sciences

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130 Citations (Scopus)

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Abstract

Candida albicans is able to proliferate in environments that vary dramatically in ambient pH, a trait required for colonising niches such as the stomach, vaginal mucosal and the GI tract. Here we show that growth in acidic environments involves cell wall remodelling which results in enhanced chitin and β-glucan exposure at the cell wall periphery. Unmasking of the underlying immuno-stimulatory β-glucan in acidic environments enhanced innate immune recognition of C. albicans by macrophages and neutrophils, and induced a stronger proinflammatory cytokine response, driven through the C-type lectin-like receptor, Dectin-1. This enhanced inflammatory response resulted in significant recruitment of neutrophils in an intraperitoneal model of infection, a hallmark of symptomatic vaginal colonisation. Enhanced chitin exposure resulted from reduced expression of the cell wall chitinase Cht2, via a Bcr1-Rim101 dependent signalling cascade, while increased β-glucan exposure was regulated via a non-canonical signalling pathway. We propose that this “unmasking” of the cell wall may induce non-protective hyper activation of the immune system during growth in acidic niches, and may attribute to symptomatic vaginal infection.

Original language	English
Article number	e1006403
Journal	PLoS Pathogens
Volume	13
Issue number	5
Early online date	22 May 2017
DOIs	https://doi.org/10.1371/journal.ppat.1006403
Publication status	Published - 2017

Bibliographical note

We would like to acknowledge Professor Gordon Brown, University of Aberdeen for providing Fc-Dectin-1 and Dectin-1 expressing fibroblast cell lines, Professor David Williams, East Tennessee State University, for providing glucan phosphate, the Candida community for strains and reagents, the Microscopy and Histology Core facility in the Institute of Medical Sciences, University of Aberdeen where the high pressure freezing was performed, staff at the University of Aberdeen Medical Research Facility, Raif Yuecel and Linda Duncan in the Iain
Fraser Cytometry Centre (Aberdeen University) for their expert help with the cytometry experiments, and all members of the host and pathogen interaction (HAPI) group at the University of Birmingham for fruitful discussions.

Funding: RAH, SLS: This work was supported by the Medical Research Council (MR/L00903X/1) (www.mrc.ac.uk). ERB: This work was supported by the UK Biotechnology and Biological Research Council (BB/M014525/1) (www.bbsrc.ac.uk). DMM: This work was supported by UK National Centre for the Replacement, Refinement and Reduction of Animals in Research (NC/K000306/1) (www.nc3rs.org.uk). ERB and DMM: This work was supported by the MRC Centre for Medical Mycology and the University of Aberdeen (MR/N006364/1). MDL is supported by the following funding sources MRC (MR/J008239/1) and the University of Aberdeen. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

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10.1371/journal.ppat.1006403Licence: CC BY

Adaptation of candida albicans
Copyright: © 2017 Sherrington 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. https://creativecommons.org/licenses/by/4.0/
Final published version, 18.3 MBLicence: CC BY

Donna MacCallum
Person: Academic Related - Management

Iain Fraser Cytometry Centre
Andrea Holme (Manager), Linda Duncan (Senior Application Scientist), Ailsa Laird (Technician) & Kate Burgoyne (Technician)
Institute of Medical Sciences
Research Facilities: Facility

Cite this

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title = "Adaptation of Candida albicans to environmental pH induces cell wall remodelling and enhances innate immune recognition",

abstract = "Candida albicans is able to proliferate in environments that vary dramatically in ambient pH, a trait required for colonising niches such as the stomach, vaginal mucosal and the GI tract. Here we show that growth in acidic environments involves cell wall remodelling which results in enhanced chitin and β-glucan exposure at the cell wall periphery. Unmasking of the underlying immuno-stimulatory β-glucan in acidic environments enhanced innate immune recognition of C. albicans by macrophages and neutrophils, and induced a stronger proinflammatory cytokine response, driven through the C-type lectin-like receptor, Dectin-1. This enhanced inflammatory response resulted in significant recruitment of neutrophils in an intraperitoneal model of infection, a hallmark of symptomatic vaginal colonisation. Enhanced chitin exposure resulted from reduced expression of the cell wall chitinase Cht2, via a Bcr1-Rim101 dependent signalling cascade, while increased β-glucan exposure was regulated via a non-canonical signalling pathway. We propose that this “unmasking” of the cell wall may induce non-protective hyper activation of the immune system during growth in acidic niches, and may attribute to symptomatic vaginal infection.",

author = "Sherrington, {Sarah L.} and Eleanor Sorsby and Nabeel Mahtey and Pizga Kumwenda and Megan Lenardon and Ian Brown and Elizabeth Ballou and MacCallum, {Donna M} and Hall, {Rebecca A.}",

note = "We would like to acknowledge Professor Gordon Brown, University of Aberdeen for providing Fc-Dectin-1 and Dectin-1 expressing fibroblast cell lines, Professor David Williams, East Tennessee State University, for providing glucan phosphate, the Candida community for strains and reagents, the Microscopy and Histology Core facility in the Institute of Medical Sciences, University of Aberdeen where the high pressure freezing was performed, staff at the University of Aberdeen Medical Research Facility, Raif Yuecel and Linda Duncan in the Iain Fraser Cytometry Centre (Aberdeen University) for their expert help with the cytometry experiments, and all members of the host and pathogen interaction (HAPI) group at the University of Birmingham for fruitful discussions. Funding: RAH, SLS: This work was supported by the Medical Research Council (MR/L00903X/1) (www.mrc.ac.uk). ERB: This work was supported by the UK Biotechnology and Biological Research Council (BB/M014525/1) (www.bbsrc.ac.uk). DMM: This work was supported by UK National Centre for the Replacement, Refinement and Reduction of Animals in Research (NC/K000306/1) (www.nc3rs.org.uk). ERB and DMM: This work was supported by the MRC Centre for Medical Mycology and the University of Aberdeen (MR/N006364/1). MDL is supported by the following funding sources MRC (MR/J008239/1) and the University of Aberdeen. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript",

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doi = "10.1371/journal.ppat.1006403",

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AU - Sherrington, Sarah L.

AU - Sorsby, Eleanor

AU - Mahtey, Nabeel

AU - Kumwenda, Pizga

AU - Lenardon, Megan

AU - Brown, Ian

AU - Ballou, Elizabeth

AU - MacCallum, Donna M

AU - Hall, Rebecca A.

N1 - We would like to acknowledge Professor Gordon Brown, University of Aberdeen for providing Fc-Dectin-1 and Dectin-1 expressing fibroblast cell lines, Professor David Williams, East Tennessee State University, for providing glucan phosphate, the Candida community for strains and reagents, the Microscopy and Histology Core facility in the Institute of Medical Sciences, University of Aberdeen where the high pressure freezing was performed, staff at the University of Aberdeen Medical Research Facility, Raif Yuecel and Linda Duncan in the Iain Fraser Cytometry Centre (Aberdeen University) for their expert help with the cytometry experiments, and all members of the host and pathogen interaction (HAPI) group at the University of Birmingham for fruitful discussions. Funding: RAH, SLS: This work was supported by the Medical Research Council (MR/L00903X/1) (www.mrc.ac.uk). ERB: This work was supported by the UK Biotechnology and Biological Research Council (BB/M014525/1) (www.bbsrc.ac.uk). DMM: This work was supported by UK National Centre for the Replacement, Refinement and Reduction of Animals in Research (NC/K000306/1) (www.nc3rs.org.uk). ERB and DMM: This work was supported by the MRC Centre for Medical Mycology and the University of Aberdeen (MR/N006364/1). MDL is supported by the following funding sources MRC (MR/J008239/1) and the University of Aberdeen. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

PY - 2017

Y1 - 2017

N2 - Candida albicans is able to proliferate in environments that vary dramatically in ambient pH, a trait required for colonising niches such as the stomach, vaginal mucosal and the GI tract. Here we show that growth in acidic environments involves cell wall remodelling which results in enhanced chitin and β-glucan exposure at the cell wall periphery. Unmasking of the underlying immuno-stimulatory β-glucan in acidic environments enhanced innate immune recognition of C. albicans by macrophages and neutrophils, and induced a stronger proinflammatory cytokine response, driven through the C-type lectin-like receptor, Dectin-1. This enhanced inflammatory response resulted in significant recruitment of neutrophils in an intraperitoneal model of infection, a hallmark of symptomatic vaginal colonisation. Enhanced chitin exposure resulted from reduced expression of the cell wall chitinase Cht2, via a Bcr1-Rim101 dependent signalling cascade, while increased β-glucan exposure was regulated via a non-canonical signalling pathway. We propose that this “unmasking” of the cell wall may induce non-protective hyper activation of the immune system during growth in acidic niches, and may attribute to symptomatic vaginal infection.

AB - Candida albicans is able to proliferate in environments that vary dramatically in ambient pH, a trait required for colonising niches such as the stomach, vaginal mucosal and the GI tract. Here we show that growth in acidic environments involves cell wall remodelling which results in enhanced chitin and β-glucan exposure at the cell wall periphery. Unmasking of the underlying immuno-stimulatory β-glucan in acidic environments enhanced innate immune recognition of C. albicans by macrophages and neutrophils, and induced a stronger proinflammatory cytokine response, driven through the C-type lectin-like receptor, Dectin-1. This enhanced inflammatory response resulted in significant recruitment of neutrophils in an intraperitoneal model of infection, a hallmark of symptomatic vaginal colonisation. Enhanced chitin exposure resulted from reduced expression of the cell wall chitinase Cht2, via a Bcr1-Rim101 dependent signalling cascade, while increased β-glucan exposure was regulated via a non-canonical signalling pathway. We propose that this “unmasking” of the cell wall may induce non-protective hyper activation of the immune system during growth in acidic niches, and may attribute to symptomatic vaginal infection.

U2 - 10.1371/journal.ppat.1006403

DO - 10.1371/journal.ppat.1006403

M3 - Article

SN - 1553-7366

VL - 13

JO - PLoS Pathogens

JF - PLoS Pathogens

IS - 5

M1 - e1006403

ER -

Adaptation of Candida albicans to environmental pH induces cell wall remodelling and enhances innate immune recognition

Abstract

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