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.
Highlights
The opportunistic fungal pathogen Candida albicans is a commensal in up to 80% of the population, and can cause superficial mucosal infections in healthy individuals [1, 2] and invasive disease in immune supressed patients [3, 4]
One of the most important environmental signals for opportunistic pathogens is ambient pH, with changes in external pH resulting in phenotypic, metabolic and physical changes in fungi and bacteria (i.e. E. coli, Salmonella, Aspergillus, Candida)
C. albicans is able to grow in media ranging from pH2 to pH10, and C. albicans has been isolated from a range of anatomical sites that vary dramatically in ambient pH including the stomach [7], vagina [8] and the oral mucosa [9], suggesting that adaptation to environmental pH is key to the pathogenicity of C. albicans
Summary
The opportunistic fungal pathogen Candida albicans is a commensal in up to 80% of the population, and can cause superficial mucosal infections in healthy individuals [1, 2] and invasive disease in immune supressed patients [3, 4]. One attribute of C. albicans that has made it such a successful opportunistic pathogen is its ability to adapt and proliferate in a broad range of host environments. C. albicans is able to grow in media ranging from pH2 to pH10, and C. albicans has been isolated from a range of anatomical sites that vary dramatically in ambient pH including the stomach (pH2) [7], vagina (pH4-5) [8] and the oral mucosa (pH6) [9], suggesting that adaptation to environmental pH is key to the pathogenicity of C. albicans. The impact environmental adaptation has on the structure and composition of the fungal cell wall, the first point of contact between the fungus and host, is not well defined
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