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.
authors.affiliation: Aberdeen Fungal Group, MRC Centre for Medical Mycology, School of Medicine, Medical Sciences and Nutrition, Institute of Medical Sciences, University of Aberdeen, Foresterhill, Aberdeen AB25 2ZD, UK.
authors.forename: Elizabeth R
authors.identifier: http://orcid.org/0000-0001-8051-2302
authors.initials: ER
authors.lastname: Ballou
authors.affiliation: Aberdeen Fungal Group, MRC Centre for Medical Mycology, School of Medicine, Medical Sciences and Nutrition, Institute of Medical Sciences, University of Aberdeen, Foresterhill, Aberdeen AB25 2ZD, UK.
authors.forename: Gabriela M
authors.initials: GM
authors.lastname: Avelar
authors.affiliation: Aberdeen Fungal Group, MRC Centre for Medical Mycology, School of Medicine, Medical Sciences and Nutrition, Institute of Medical Sciences, University of Aberdeen, Foresterhill, Aberdeen AB25 2ZD, UK.
authors.forename: Delma S
authors.initials: DS
authors.lastname: Childers
authors.affiliation: Aberdeen Fungal Group, MRC Centre for Medical Mycology, School of Medicine, Medical Sciences and Nutrition, Institute of Medical Sciences, University of Aberdeen, Foresterhill, Aberdeen AB25 2ZD, UK.
authors.forename: Joanna
authors.initials: J
authors.lastname: Mackie
authors.affiliation: Aberdeen Fungal Group, MRC Centre for Medical Mycology, School of Medicine, Medical Sciences and Nutrition, Institute of Medical Sciences, University of Aberdeen, Foresterhill, Aberdeen AB25 2ZD, UK.
authors.forename: Judith M
authors.initials: JM
authors.lastname: Bain
authors.affiliation: Aberdeen Fungal Group, MRC Centre for Medical Mycology, School of Medicine, Medical Sciences and Nutrition, Institute of Medical Sciences, University of Aberdeen, Foresterhill, Aberdeen AB25 2ZD, UK.
authors.forename: Jeanette
authors.initials: J
authors.lastname: Wagener
authors.affiliation: Aberdeen Fungal Group, MRC Centre for Medical Mycology, School of Medicine, Medical Sciences and Nutrition, Institute of Medical Sciences, University of Aberdeen, Foresterhill, Aberdeen AB25 2ZD, UK.
authors.forename: Stavroula L
authors.initials: SL
authors.lastname: Kastora
authors.affiliation: Aberdeen Fungal Group, MRC Centre for Medical Mycology, School of Medicine, Medical Sciences and Nutrition, Institute of Medical Sciences, University of Aberdeen, Foresterhill, Aberdeen AB25 2ZD, UK.
authors.forename: Mirela D
authors.initials: MD
authors.lastname: Panea
authors.affiliation: Aberdeen Fungal Group, MRC Centre for Medical Mycology, School of Medicine, Medical Sciences and Nutrition, Institute of Medical Sciences, University of Aberdeen, Foresterhill, Aberdeen AB25 2ZD, UK.
authors.forename: Sarah E
authors.initials: SE
authors.lastname: Hardison
authors.affiliation: Aberdeen Fungal Group, MRC Centre for Medical Mycology, School of Medicine, Medical Sciences and Nutrition, Institute of Medical Sciences, University of Aberdeen, Foresterhill, Aberdeen AB25 2ZD, UK.
authors.forename: Louise A
authors.initials: LA
authors.lastname: Walker
authors.affiliation: Aberdeen Fungal Group, MRC Centre for Medical Mycology, School of Medicine, Medical Sciences and Nutrition, Institute of Medical Sciences, University of Aberdeen, Foresterhill, Aberdeen AB25 2ZD, UK.
authors.forename: Lars P
authors.initials: LP
authors.lastname: Erwig
authors.affiliation: Aberdeen Fungal Group, MRC Centre for Medical Mycology, School of Medicine, Medical Sciences and Nutrition, Institute of Medical Sciences, University of Aberdeen, Foresterhill, Aberdeen AB25 2ZD, UK.
authors.forename: Carol A
authors.identifier: http://orcid.org/0000-0003-0761-1755
authors.initials: CA
authors.lastname: Munro
authors.affiliation: Aberdeen Fungal Group, MRC Centre for Medical Mycology, School of Medicine, Medical Sciences and Nutrition, Institute of Medical Sciences, University of Aberdeen, Foresterhill, Aberdeen AB25 2ZD, UK.
authors.forename: Neil A R
authors.initials: NA
authors.lastname: Gow
authors.affiliation: Aberdeen Fungal Group, MRC Centre for Medical Mycology, School of Medicine, Medical Sciences and Nutrition, Institute of Medical Sciences, University of Aberdeen, Foresterhill, Aberdeen AB25 2ZD, UK.
authors.forename: Gordon D
authors.initials: GD
authors.lastname: Brown
authors.affiliation: Aberdeen Fungal Group, MRC Centre for Medical Mycology, School of Medicine, Medical Sciences and Nutrition, Institute of Medical Sciences, University of Aberdeen, Foresterhill, Aberdeen AB25 2ZD, UK.
authors.forename: Donna M
authors.identifier: http://orcid.org/0000-0003-4833-0378
authors.initials: DM
authors.lastname: MacCallum
authors.affiliation: Aberdeen Fungal Group, MRC Centre for Medical Mycology, School of Medicine, Medical Sciences and Nutrition, Institute of Medical Sciences, University of Aberdeen, Foresterhill, Aberdeen AB25 2ZD, UK.
authors.forename: Alistair J P
authors.initials: AJ
authors.lastname: Brown
mesh_terms: D002176:Candida albicans / Q000276:immunology* / Q000378:metabolism*; D006031:Glycosylation; D057131:Immune Evasion; D019344:Lactic Acid / Q000378:metabolism*; D008565:Membrane Proteins / Q000378:metabolism*; D047071:beta-Glucans / Q000378:metabolism*
chemical_list: D008565:Membrane Proteins; D047071:beta-Glucans; D019344:Lactic Acid