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

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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 languageEnglish
Article numbere1006403
JournalPLoS Pathogens
Volume13
Issue number5
Early online date22 May 2017
DOIs
Publication statusPublished - 2017

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Candida albicans
Cell Wall
Glucans
Chitin
C-Type Lectins
Chitinases
Neutrophil Infiltration
Growth
Infection
Gastrointestinal Tract
Immune System
Stomach
Neutrophils
Macrophages
Cytokines

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Sherrington, S. L., Sorsby, E., Mahtey, N., Kumwenda, P., Lenardon, M., Brown, I., ... Hall, R. A. (2017). Adaptation of Candida albicans to environmental pH induces cell wall remodelling and enhances innate immune recognition. PLoS Pathogens, 13(5), [e1006403]. https://doi.org/10.1371/journal.ppat.1006403

Adaptation of Candida albicans to environmental pH induces cell wall remodelling and enhances innate immune recognition. / Sherrington, Sarah L.; Sorsby, Eleanor; Mahtey, Nabeel ; Kumwenda, Pizga; Lenardon, Megan; Brown, Ian; Ballou, Elizabeth; MacCallum, Donna M; Hall, Rebecca A. .

In: PLoS Pathogens, Vol. 13, No. 5, e1006403, 2017.

Research output: Contribution to journalArticle

Sherrington, SL, Sorsby, E, Mahtey, N, Kumwenda, P, Lenardon, M, Brown, I, Ballou, E, MacCallum, DM & Hall, RA 2017, 'Adaptation of Candida albicans to environmental pH induces cell wall remodelling and enhances innate immune recognition', PLoS Pathogens, vol. 13, no. 5, e1006403. https://doi.org/10.1371/journal.ppat.1006403
Sherrington, Sarah L. ; Sorsby, Eleanor ; Mahtey, Nabeel ; Kumwenda, Pizga ; Lenardon, Megan ; Brown, Ian ; Ballou, Elizabeth ; MacCallum, Donna M ; Hall, Rebecca A. . / Adaptation of Candida albicans to environmental pH induces cell wall remodelling and enhances innate immune recognition. In: PLoS Pathogens. 2017 ; Vol. 13, No. 5.
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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.",
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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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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

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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.

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