Interactions of Extracellular Vesicles from Pathogenic Fungi with Innate Leukocytes

Freitas, Mateus Silveira; Pessoni, André Moreira; Coelho, Carolina; Bonato, Vânia Luiza Deperon; Rodrigues, Márcio L.; Casadevall, Arturo; Almeida, Fausto

doi:10.1007/978-3-030-83391-6_9

Cited by 6 publications

(8 citation statements)

References 150 publications

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“…They are recognized as pathogen-associated molecular patterns (PAMPs) by the pattern recognition receptors (PRRs) of the host's innate immune system. Therefore, fungal EVs could modulate the activation of the immune response 29 which may depend either on the fungal species or the EVs structure and content 30 . The studies on the immunomodulatory properties of fungal EVs suggest that they can play an important role in host-fungal communication, exerting a plethora of different effects that range from the enhancement of the host immune response to a control of the fungal infection or tolerance by the immune system [31][32][33][34] .…”

Section: Discussionmentioning

confidence: 99%

Characterization and immunomodulatory potential of extracellular vesicles from non-pathogenic yeast strains

Nenciarini,

Amoriello,

Bacci

et al. 2023

Preprint

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Extracellular vesicles (EVs) are lipid-bilayered particles, containing various biomolecules, including nucleic acids, lipids, and proteins, released by cells from all the domains of life and performing multiple communication functions. Evidence suggests that the interaction between host immune cells and fungal EVs induces modulation of the immune system. Most of the studies on fungal EVs have been conducted in the context of fungal infections; therefore, there is still a knowledge gap regarding EVs produced by non-pathogenic yeasts. In this work, we characterized EVs obtained by Saccharomyces cerevisiae and Pichia fermentans strains isolated from a fermented milk product with probiotic properties. The immunomodulation abilities of EVs produced by these strains have been studied in vitro through immune assays after internalization from human monocyte-derived dendritic cells. Results showed a significant reduction in antigen presentation activity of dendritic cells treated with the fermented milk EVs. The small RNA fraction of EVs contained mainly yeast mRNA sequences, with a few molecular functions enriched in strains of two different species isolated from the fermented milk. Our results suggest that one of the mechanisms behind the anti-inflammatory properties of probiotic foods could be mediated by the interactions of human immune cells with yeast EVs.

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Section: Discussionmentioning

confidence: 99%

Characterization and immunomodulatory potential of extracellular vesicles from non-pathogenic yeast strains

Nenciarini,

Amoriello,

Bacci

et al. 2023

Preprint

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“…Taken together, the studies on the immunomodulatory properties of fungal EVs show that they play an important role in host-fungal communication, both during infection and commensalism dynamics. Fungal EVs are recognised by the host cell and activate an immune response that may depend on both the fungal species and the EV composition [185]. Here, we present the current data on virulence factors contained in fungal EVs, as well as their immunomodulation properties.…”

Section: Fungal Evs and Interactions With Host Immunitymentioning

confidence: 95%

“…Extracellular vesicles are well-known mediators of the immune response [86,182,183] thanks to their immunogenic cargo. Several studies, previously reviewed [4,19,26,[184][185][186], explored the immunomodulation potential of EVs from both pathogenic and non-pathogenic fungal species. It is now well established that fungal EV cargos are recognised as pathogenassociated molecular patterns (PAMPs) by the pattern recognition receptors (PRRs) of the host innate immune system, and that therefore fungal EVs could modulate the activation of host immunity [187].…”

Section: Fungal Evs and Interactions With Host Immunitymentioning

confidence: 99%

“…Many of these virulence factors, packed into EVs such that they were called "virulence bags" in early studies [53,65], are delivered to target host cells. Here, we provide an overview of the virulence factors often observed to be associated with pathogenic fungal EVs and their mechanism of action, both of which have been exhaustively reviewed elsewhere [185].…”

Section: Promoting Infectionsmentioning

confidence: 99%

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Immunomodulatory Potential of Fungal Extracellular Vesicles: Insights for Therapeutic Applications

Nenciarini,

Cavalieri

2023

Biomolecules

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Extracellular vesicles (EVs) are membranous vesicular organelles that perform a variety of biological functions including cell communication across different biological kingdoms. EVs of mammals and, to a lesser extent, bacteria have been deeply studied over the years, whereas investigations of fungal EVs are still in their infancy. Fungi, encompassing both yeast and filamentous forms, are increasingly recognized for their production of extracellular vesicles (EVs) containing a wealth of proteins, lipids, and nucleic acids. These EVs play pivotal roles in orchestrating fungal communities, bolstering pathogenicity, and mediating interactions with the environment. Fungal EVs have emerged as promising candidates for innovative applications, not only in the management of mycoses but also as carriers for therapeutic molecules. Yet, numerous questions persist regarding fungal EVs, including their mechanisms of generation, release, cargo regulation, and discharge. This comprehensive review delves into the present state of knowledge regarding fungal EVs and provides fresh insights into the most recent hypotheses on the mechanisms driving their immunomodulatory properties. Furthermore, we explore the considerable potential of fungal EVs in the realms of medicine and biotechnology. In the foreseeable future, engineered fungal cells may serve as vehicles for tailoring cargo- and antigen-specific EVs, positioning them as invaluable biotechnological tools for diverse medical applications, such as vaccines and drug delivery.

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“…Recently, it has been established that fungal EVs can play important functions in intercellular, interspecies, and interkingdom communication, presumably using the different molecules they transport, that is, numerous proteins, peptides, nucleic acids, lipids, and other signaling compounds [6][7][8]. In the fungi pathogenic to humans, the EVs they produce have been frequently demonstrated to be involved in interactions with different types of host cells, thus strongly contributing to microbial virulence related to the ability to initiate infection and further dissemination within the human organism [9][10][11].…”

Section: Introductionmentioning

confidence: 99%

Candida albicans Biofilm-Derived Extracellular Vesicles Are Involved in the Tolerance to Caspofungin, Biofilm Detachment, and Fungal Proteolytic Activity

Karkowska-Kuleta,

Kulig,

Bras

et al. 2023

JoF

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It has been repeatedly reported that the cells of organisms in all kingdoms of life produce nanometer-sized lipid membrane-enveloped extracellular vesicles (EVs), transporting and protecting various substances of cellular origin. While the composition of EVs produced by human pathogenic fungi has been studied in recent decades, another important challenge is the analysis of their functionality. Thus far, fungal EVs have been shown to play significant roles in intercellular communication, biofilm production, and modulation of host immune cell responses. In this study, we verified the involvement of biofilm-derived EVs produced by two different strains of Candida albicans—C. albicans SC5314 and 3147 (ATCC 10231)—in various aspects of biofilm function by examining its thickness, stability, metabolic activity, and cell viability in the presence of EVs and the antifungal drug caspofungin. Furthermore, the proteolytic activity against the kininogen-derived antimicrobial peptide NAT26 was confirmed by HPLC analysis for C. albicans EVs that are known to carry, among others, particular members of the secreted aspartic proteinases (Saps) family. In conclusion, EVs derived from C. albicans biofilms were shown to be involved in biofilm tolerance to caspofungin, biofilm detachment, and fungal proteolytic activity.

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Interactions of Extracellular Vesicles from Pathogenic Fungi with Innate Leukocytes

Cited by 6 publications

References 150 publications

Characterization and immunomodulatory potential of extracellular vesicles from non-pathogenic yeast strains

Characterization and immunomodulatory potential of extracellular vesicles from non-pathogenic yeast strains

Immunomodulatory Potential of Fungal Extracellular Vesicles: Insights for Therapeutic Applications

Candida albicans Biofilm-Derived Extracellular Vesicles Are Involved in the Tolerance to Caspofungin, Biofilm Detachment, and Fungal Proteolytic Activity

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