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Updated: May 30, 2025
A Soluble Tetrazolium-Based Reduction Assay to Evaluate the Effect of Antibodies on Candida tropicalis Biofilms
Published on: September 16, 2022
Host cell responses to Candida albicans biofilm-derived extracellular vesicles
Kamila Kulig1, Ewelina Wronowska1, Magdalena Juszczak1,2
1Department of Comparative Biochemistry and Bioanalytics, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Kraków, Poland.
Abstract:
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.
Insights
Extracellular vesicles (EVs) from Candida albicans biofilms promote inflammation and infection. These fungal EVs adhere to host cells, induce cytokine release, and attract immune cells, increasing infection severity.
Area of Science:
- Microbiology
- Immunology
- Pathogenesis
Background:
- Candida albicans is a major human fungal pathogen.
- Extracellular vesicles (EVs) from C. albicans contribute to infection by modulating host responses.
- Biofilm-derived EVs are implicated in pathogenesis, but their specific functions require further investigation.
Purpose of the Study:
- To investigate the functional properties of EVs from C. albicans biofilms in eliciting host responses.
- To determine the role of these EVs in host cell interaction and immune cell activation.
- To assess the in vivo impact of biofilm-derived EVs on host infection models.
Main Methods:
- Culturing C. albicans biofilms and isolating EVs.
- Treating human epithelial (A549) and immune cells (THP-1, monocytes, neutrophils) with EVs.
- Analyzing cytokine production, EV internalization (macropinocytosis, phagocytosis), and neutrophil chemotaxis.
- Evaluating the in vivo effect of EVs using Galleria mellonella infection model.
Main Results:
- C. albicans EVs adhered to epithelial cells and induced cytokine production in various human cell types.
- EVs were internalized by THP-1 cells via macropinocytosis and phagocytosis.
- EVs acted as chemoattractants for neutrophils.
- EVs from C. albicans SC5314 biofilms increased mortality in Galleria mellonella larvae.
Conclusions:
- C. albicans biofilm-derived EVs possess pro-inflammatory properties.
- These EVs play a significant role in the host inflammatory response during C. albicans infection.
- EVs are key mediators in C. albicans pathogenesis, influencing host cell behavior and infection outcomes.
