Fungal Extracellular Vesicles as Potential Targets for Immune Interventions

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

doi:10.1128/msphere.00747-19

Cited by 45 publications

(48 citation statements)

References 95 publications

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“…In contrast, EVs from H. capsulatum decreased both the phagocytic activity and killing rate of BMDMs (33), suggesting an immunomodulatory activity of EVs. Depending on the pathogen, the fungal EVs can intensify or attenuate the progression of the infection (14).…”

Section: Discussionmentioning

confidence: 99%

“…EVs carry tremendous molecular content, including molecules that interact with the pattern recognition receptors expressed on cells of the immune system (for example, receptors from family of C-type lectin), thereby resulting in activation of innate and/or adaptive responses and protection of the host against infection (34,35). Thus, EVs may act as key modulators of the immune response for different fungal infections, thus demonstrating the potential of these structures as possible targets for immune interventions (14).…”

Section: Discussionmentioning

confidence: 99%

“…Extracellular vesicles (EVs) are structures produced by all life domains; they range in size from 30 to 1,000 nm and are surrounded by a lipid bilayer, carry protein, lipids, polysaccharides, nucleic acids, and pigments, and are crucial in cell communication, physiology, and immunopathogenesis of fungal infections (11)(12)(13). Fungal EV cargo may influence the host-parasite relationship during fungal infections (14). In 2007, Rodrigues et al, studying Cryptococcus neoformans, initially reported production of EVs by fungi (15).…”

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confidence: 99%

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Extracellular Vesicles from Aspergillus flavus Induce M1 Polarization In Vitro

Brauer

Pessoni

Bitencourt

et al. 2020

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Aspergillus flavus, a ubiquitous and saprophytic fungus, is the second most common cause of aspergillosis worldwide. Several mechanisms contribute to the establishment of the fungal infection. Extracellular vesicles (EVs) have been described as “virulence factor delivery bags” in several fungal species, demonstrating a crucial role during the infection. In this study, we evaluated production of A. flavus EVs and their immunomodulatory functions. We verified that A. flavus EVs induce macrophages to produce inflammatory mediators, such as nitric oxide, tumor necrosis factor alpha (TNF-α), interleukin-6 (IL-6), and IL-1β. Furthermore, the A. flavus EVs enhance phagocytosis and killing by macrophages and induce M1 macrophage polarization in vitro. In addition, a prior inoculation of A. flavus EVs in Galleria mellonella larvae resulted in a protective effect against the fungal infection. Our findings suggest that A. flavus EVs are biologically active and affect the interaction between A. flavus and host immune cells, priming the innate immune system to eliminate the fungal infection. Collectively, our results suggest that A. flavus EVs play a crucial role in aspergillosis. IMPORTANCE Immunocompromised patients are susceptible to several fungal infections. The genus Aspergillus can cause increased morbidity and mortality. Developing new therapies is essential to understand the fungal biology mechanisms. Fungal EVs carry important virulence factors, thus playing pivotal roles in fungal pathophysiology. No study to date has reported EV production by Aspergillus flavus, a fungus considered to be the second most common cause of aspergillosis and relevant food contaminator found worldwide. In this study, we produced A. flavus EVs and evaluated the in vitro immunomodulatory effects of EVs on bone marrow-derived macrophages (BMDMs) and in vivo effects in a Galleria mellonella model.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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confidence: 99%

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Extracellular Vesicles from Aspergillus flavus Induce M1 Polarization In Vitro

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Pessoni

Bitencourt

et al. 2020

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“…The composition of each kind of EV derives from the cell and purpose of the vesicle realized to the media. As such, these vesicles became an important marker for diseases, including cancer, infectious diseases, renal diseases, and diabetes [16][17][18][19][20]. In order to achieve this, EVs must be characterized and analyze their confidence to be candidates for those used by humans.…”

Section: Study Of Evsmentioning

confidence: 99%

Introductory Chapter: An Overview to the Extracellular Vesicles

Gil-Bona¹,

Reales-Calderón²

2020

Extracellular Vesicles and Their Importance in Human Health

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“…It is important to mention a recent study by Freitas et al, (2019) about fungal extracellular vesicles as potential targets for immune interventions. The article reports how important the release of extracellular vesicles by fungi and about its basic cellular process.…”

Section: Fungal Infections and Immunitymentioning

confidence: 99%

Protective immune studies against fungi

Kumondorova¹,

Metiner²

2020

Journal of Istanbul Veterinary Sciences

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The immune system is the host's defence against different agents and infections. Understanding the complex and highly dynamic interactions between fungi and host cells in a tissue-specific manner is crucial to facilitate the development of new therapeutic approaches to infections. Generally fungal pathogens rarely cause diseases in immunologically competent individuals. However, commensal and non-pathogenic environmental fungi can cause life-threatening infections in individuals with immune deficiency. Understanding the molecular and cellular bases of immunity to fungi has progressed significantly over the past few years. Despite close interactions with fungi today, how the immune system protects humans and animals from fungal pathogens has not been fully elucidated compared to the immune response to bacteria or viruses. The immune system is the host's defence against various foreign proteins and infections. Understanding the complex and highly dynamic interactions between fungi and host cells is crucial for the development of new therapeutic approaches to infections. Researchers from 15 countries in Europe, Asia, Australia, North and South America have provided the last five years review and original research articles that consist of a wide range of fungal pathogens, disease, effector, regulatory cells and molecular pathways of host immune responses to fungal exposure. In this review, we summarize an outline of the recent findings, perspectives, and reviews about the complex and highly dynamic interactions between fungi and host cells and a contemporary understanding of protective immunity against fungi. This review will allow an overview of the most exciting recent advances in antifungal immunity, discoveries that will help pave the way for the development of new strategies that are seriously needed to combat these devastating diseases.

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Fungal Extracellular Vesicles as Potential Targets for Immune Interventions

Cited by 45 publications

References 95 publications

Extracellular Vesicles from Aspergillus flavus Induce M1 Polarization In Vitro

Extracellular Vesicles from Aspergillus flavus Induce M1 Polarization In Vitro

Introductory Chapter: An Overview to the Extracellular Vesicles

Protective immune studies against fungi

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