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ORIGINAL RESEARCH article

Front. Cell. Infect. Microbiol.
Sec. Fungal Pathogenesis
Volume 14 - 2024 | doi: 10.3389/fcimb.2024.1499461

Host cell responses to Candida albicans biofilm-derived extracellular vesicles

Provisionally accepted
Kamila Kulig Kamila Kulig 1Ewelina Wronowska Ewelina Wronowska 1Magdalena Juszczak Magdalena Juszczak 1,2Marcin Zawrotniak Marcin Zawrotniak 1Justyna Karkowska-Kuleta Justyna Karkowska-Kuleta 1Maria Rapala-Kozik Maria Rapala-Kozik 1*
  • 1 Department of Comparative Biochemistry and Bioanalysis, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Kraków, Lesser Poland, Poland
  • 2 Doctoral School of Exact and Natural Sciences, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Krakow, Poland

The final, formatted version of the article will be published soon.

    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 proinflammatory effect on host was observed, highlighting their significant role in the inflammatory response during C. albicans infection.

    Keywords: extracellular vesicles, Candida albicans, Biofilm, Host immune response, pathogenic fungi, Candidiasis

    Received: 20 Sep 2024; Accepted: 18 Dec 2024.

    Copyright: © 2024 Kulig, Wronowska, Juszczak, Zawrotniak, Karkowska-Kuleta and Rapala-Kozik. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Maria Rapala-Kozik, Department of Comparative Biochemistry and Bioanalysis, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Kraków, 30-387, Lesser Poland, Poland

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