Host cell responses to Candida albicans biofilm-derived extracellular vesicles

Candida albicans is a prevalent fungal pathogen responsible for infections in humans. As described recently, nanometer-sized extracellular vesicles (EVs) produced by C. albicans play a crucial role in the pathogenesis of infection by facilitating host inflammatory responses and intercellular communi...

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Main Authors: Kamila Kulig, Ewelina Wronowska, Magdalena Juszczak, Marcin Zawrotniak, Justyna Karkowska-Kuleta, Maria Rapala-Kozik
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-01-01
Series:Frontiers in Cellular and Infection Microbiology
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Online Access:https://www.frontiersin.org/articles/10.3389/fcimb.2024.1499461/full
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author Kamila Kulig
Ewelina Wronowska
Magdalena Juszczak
Magdalena Juszczak
Marcin Zawrotniak
Justyna Karkowska-Kuleta
Maria Rapala-Kozik
author_facet Kamila Kulig
Ewelina Wronowska
Magdalena Juszczak
Magdalena Juszczak
Marcin Zawrotniak
Justyna Karkowska-Kuleta
Maria Rapala-Kozik
author_sort Kamila Kulig
collection DOAJ
description Candida albicans is a prevalent fungal pathogen responsible for infections in humans. As described recently, nanometer-sized extracellular vesicles (EVs) produced by C. albicans play a crucial role in the pathogenesis of infection by facilitating host inflammatory responses and intercellular communication. This study investigates the functional properties of EVs released by biofilms formed by two C. albicans strains—3147 (ATCC 10231) and SC5314—in eliciting host responses. We demonstrate the capability of C. albicans EVs to trigger reactions in human epithelial and immune cells. The involvement of EVs in pathogenesis was evidenced from the initial stages of infection, specifically in adherence to epithelial cells. We further established the capacity of these EVs to induce cytokine production in the epithelial A549 cell line, THP-1 macrophage-like cells, and blood-derived monocytes differentiated into macrophages. Internalization of EVs by THP-1 macrophage-like cells was confirmed, identifying macropinocytosis and phagocytosis as the most probable mechanisms, as demonstrated using various inhibitors that target potential vesicle uptake pathways in human cells. Additionally, C. albicans EVs and their cargo were identified as chemoattractants for blood-derived neutrophils. After verification of the in vivo effect of biofilm-derived EVs on the host, using Galleria mellonella larvae as an alternative model, it was demonstrated that vesicles from C. albicans SC5314 increased mortality in the injected larvae. In conclusion, for both types of EVs a predominantly pro-inflammatory effect on host was observed, highlighting their significant role in the inflammatory response during C. albicans infection.
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spelling doaj-art-4236b081306f4d6089b2db780da624422025-01-14T06:10:20ZengFrontiers Media S.A.Frontiers in Cellular and Infection Microbiology2235-29882025-01-011410.3389/fcimb.2024.14994611499461Host cell responses to Candida albicans biofilm-derived extracellular vesiclesKamila Kulig0Ewelina Wronowska1Magdalena Juszczak2Magdalena Juszczak3Marcin Zawrotniak4Justyna Karkowska-Kuleta5Maria Rapala-Kozik6Department of Comparative Biochemistry and Bioanalytics, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Kraków, PolandDepartment of Comparative Biochemistry and Bioanalytics, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Kraków, PolandDepartment of Comparative Biochemistry and Bioanalytics, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Kraków, PolandDoctoral School of Exact and Natural Sciences, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Kraków, PolandDepartment of Comparative Biochemistry and Bioanalytics, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Kraków, PolandDepartment of Comparative Biochemistry and Bioanalytics, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Kraków, PolandDepartment of Comparative Biochemistry and Bioanalytics, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Kraków, PolandCandida albicans is a prevalent fungal pathogen responsible for infections in humans. As described recently, nanometer-sized extracellular vesicles (EVs) produced by C. albicans play a crucial role in the pathogenesis of infection by facilitating host inflammatory responses and intercellular communication. This study investigates the functional properties of EVs released by biofilms formed by two C. albicans strains—3147 (ATCC 10231) and SC5314—in eliciting host responses. We demonstrate the capability of C. albicans EVs to trigger reactions in human epithelial and immune cells. The involvement of EVs in pathogenesis was evidenced from the initial stages of infection, specifically in adherence to epithelial cells. We further established the capacity of these EVs to induce cytokine production in the epithelial A549 cell line, THP-1 macrophage-like cells, and blood-derived monocytes differentiated into macrophages. Internalization of EVs by THP-1 macrophage-like cells was confirmed, identifying macropinocytosis and phagocytosis as the most probable mechanisms, as demonstrated using various inhibitors that target potential vesicle uptake pathways in human cells. Additionally, C. albicans EVs and their cargo were identified as chemoattractants for blood-derived neutrophils. After verification of the in vivo effect of biofilm-derived EVs on the host, using Galleria mellonella larvae as an alternative model, it was demonstrated that vesicles from C. albicans SC5314 increased mortality in the injected larvae. In conclusion, for both types of EVs a predominantly pro-inflammatory effect on host was observed, highlighting their significant role in the inflammatory response during C. albicans infection.https://www.frontiersin.org/articles/10.3389/fcimb.2024.1499461/fullextracellular vesiclesCandida albicansbiofilmhost immune responsepathogenic fungicandidiasis
spellingShingle Kamila Kulig
Ewelina Wronowska
Magdalena Juszczak
Magdalena Juszczak
Marcin Zawrotniak
Justyna Karkowska-Kuleta
Maria Rapala-Kozik
Host cell responses to Candida albicans biofilm-derived extracellular vesicles
Frontiers in Cellular and Infection Microbiology
extracellular vesicles
Candida albicans
biofilm
host immune response
pathogenic fungi
candidiasis
title Host cell responses to Candida albicans biofilm-derived extracellular vesicles
title_full Host cell responses to Candida albicans biofilm-derived extracellular vesicles
title_fullStr Host cell responses to Candida albicans biofilm-derived extracellular vesicles
title_full_unstemmed Host cell responses to Candida albicans biofilm-derived extracellular vesicles
title_short Host cell responses to Candida albicans biofilm-derived extracellular vesicles
title_sort host cell responses to candida albicans biofilm derived extracellular vesicles
topic extracellular vesicles
Candida albicans
biofilm
host immune response
pathogenic fungi
candidiasis
url https://www.frontiersin.org/articles/10.3389/fcimb.2024.1499461/full
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