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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51 Citations (Scopus)
9 Downloads (Pure)

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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    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

    Sherrington, S. L., Sorsby, E., Mahtey, N., Kumwenda, P., Lenardon, M., Brown, I., Ballou, E., MacCallum, D. M., & 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