The symptoms of infectious diseases are frequently caused by an over­zealous host immune response against the invading microorganism, rather than by the microorganism itself. This is the case for one of the most common mucosal infection, vulvovaginal candidiasis (VVC), where the yeast Candida albicans triggers a non‐protective influx of host immune cells, resulting in aggressive local inflammation and symptomatic disease. The aim of our study was to investigate the role of the zincophore Pra1 in VVC immunopathology. Pra1 is a secreted C. albicans zinc binding protein released during zinc limitation and used by the fungus to forage for this essential micronutrient from the environment. In vitro tissue culture systems, a murine model of experimental vaginal candidiasis and vaginal samples from VVC patients were used to evaluate the role of Pra1 in immunopathology during VVC. Our results show that Pra1 induced neutrophil migration, is expressed at both, neutral and acidic pH by C. albicans during infection of vaginal epithelial cells and the expression was repressed by the addition of zinc. Robust PRA1 expression was also found in clinical vaginal samples and a strong correlation between PRA1 expression and the neutrophil­activating cytokine IL­8 has been demonstrated. In an experimental murine model of VVC, deletion of C. albicans PRA1 abrogated inflammation without affecting fungal burden. These data demonstrate that the zincophore Pra1 is expressed during the VVC and can act as a potent neutrophil chemoattractant molecule, driving inflammation.

The Candida albicans Pra1 zincophore promotes neutrophils recruitment and inflammation during vulvovaginal candidiasis / Roselletti, E.; Pericolini, E.; Sala, A.; Comar, M.; De Seta, F.; Wilson, D.. - (2022). (Intervento presentato al convegno Molecular Mechanisms of Host-pathogen Interactions and Virulence in Human Fungal Pathogens tenutosi a La Colle sur Loup, France nel 14-20 May 2022).

The Candida albicans Pra1 zincophore promotes neutrophils recruitment and inflammation during vulvovaginal candidiasis

Pericolini E.;
2022

Abstract

The symptoms of infectious diseases are frequently caused by an over­zealous host immune response against the invading microorganism, rather than by the microorganism itself. This is the case for one of the most common mucosal infection, vulvovaginal candidiasis (VVC), where the yeast Candida albicans triggers a non‐protective influx of host immune cells, resulting in aggressive local inflammation and symptomatic disease. The aim of our study was to investigate the role of the zincophore Pra1 in VVC immunopathology. Pra1 is a secreted C. albicans zinc binding protein released during zinc limitation and used by the fungus to forage for this essential micronutrient from the environment. In vitro tissue culture systems, a murine model of experimental vaginal candidiasis and vaginal samples from VVC patients were used to evaluate the role of Pra1 in immunopathology during VVC. Our results show that Pra1 induced neutrophil migration, is expressed at both, neutral and acidic pH by C. albicans during infection of vaginal epithelial cells and the expression was repressed by the addition of zinc. Robust PRA1 expression was also found in clinical vaginal samples and a strong correlation between PRA1 expression and the neutrophil­activating cytokine IL­8 has been demonstrated. In an experimental murine model of VVC, deletion of C. albicans PRA1 abrogated inflammation without affecting fungal burden. These data demonstrate that the zincophore Pra1 is expressed during the VVC and can act as a potent neutrophil chemoattractant molecule, driving inflammation.
2022
Molecular Mechanisms of Host-pathogen Interactions and Virulence in Human Fungal Pathogens
La Colle sur Loup, France
14-20 May 2022
Roselletti, E.; Pericolini, E.; Sala, A.; Comar, M.; De Seta, F.; Wilson, D.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11380/1274499
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