Extracellular Vesicles from <named-content content-type="genus-species">Aspergillus flavus</named-content> Induce M1 Polarization <italic toggle="yes">In Vitro</italic>

ABSTRACT 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 fu...

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Autores principales:	Verônica S. Brauer, André M. Pessoni, Tamires A. Bitencourt, Renato G. de Paula, Liliana de Oliveira Rocha, Gustavo H. Goldman, Fausto Almeida
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2020
Materias:	Aspergillus flavus extracellular vesicles macrophage cytokine phagocytosis killing Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/34c1641a49c042dba5167a8eae0f48ac
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spelling	oai:doaj.org-article:34c1641a49c042dba5167a8eae0f48ac2021-11-15T15:30:14ZExtracellular Vesicles from <named-content content-type="genus-species">Aspergillus flavus</named-content> Induce M1 Polarization <italic toggle="yes">In Vitro</italic>10.1128/mSphere.00190-202379-5042https://doaj.org/article/34c1641a49c042dba5167a8eae0f48ac2020-06-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mSphere.00190-20https://doaj.org/toc/2379-5042ABSTRACT 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.Verônica S. BrauerAndré M. PessoniTamires A. BitencourtRenato G. de PaulaLiliana de Oliveira RochaGustavo H. GoldmanFausto AlmeidaAmerican Society for MicrobiologyarticleAspergillus flavusextracellular vesiclesmacrophagecytokinephagocytosiskillingMicrobiologyQR1-502ENmSphere, Vol 5, Iss 3 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	Aspergillus flavus extracellular vesicles macrophage cytokine phagocytosis killing Microbiology QR1-502
spellingShingle	Aspergillus flavus extracellular vesicles macrophage cytokine phagocytosis killing Microbiology QR1-502 Verônica S. Brauer André M. Pessoni Tamires A. Bitencourt Renato G. de Paula Liliana de Oliveira Rocha Gustavo H. Goldman Fausto Almeida Extracellular Vesicles from <named-content content-type="genus-species">Aspergillus flavus</named-content> Induce M1 Polarization <italic toggle="yes">In Vitro</italic>
description	ABSTRACT 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.
format	article
author	Verônica S. Brauer André M. Pessoni Tamires A. Bitencourt Renato G. de Paula Liliana de Oliveira Rocha Gustavo H. Goldman Fausto Almeida
author_facet	Verônica S. Brauer André M. Pessoni Tamires A. Bitencourt Renato G. de Paula Liliana de Oliveira Rocha Gustavo H. Goldman Fausto Almeida
author_sort	Verônica S. Brauer
title	Extracellular Vesicles from <named-content content-type="genus-species">Aspergillus flavus</named-content> Induce M1 Polarization <italic toggle="yes">In Vitro</italic>
title_short	Extracellular Vesicles from <named-content content-type="genus-species">Aspergillus flavus</named-content> Induce M1 Polarization <italic toggle="yes">In Vitro</italic>
title_full	Extracellular Vesicles from <named-content content-type="genus-species">Aspergillus flavus</named-content> Induce M1 Polarization <italic toggle="yes">In Vitro</italic>
title_fullStr	Extracellular Vesicles from <named-content content-type="genus-species">Aspergillus flavus</named-content> Induce M1 Polarization <italic toggle="yes">In Vitro</italic>
title_full_unstemmed	Extracellular Vesicles from <named-content content-type="genus-species">Aspergillus flavus</named-content> Induce M1 Polarization <italic toggle="yes">In Vitro</italic>
title_sort	extracellular vesicles from <named-content content-type="genus-species">aspergillus flavus</named-content> induce m1 polarization <italic toggle="yes">in vitro</italic>
publisher	American Society for Microbiology
publishDate	2020
url	https://doaj.org/article/34c1641a49c042dba5167a8eae0f48ac
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Extracellular Vesicles from <named-content content-type="genus-species">Aspergillus flavus</named-content> Induce M1 Polarization <italic toggle="yes">In Vitro</italic>

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