Extracellular Vesicles from Aspergillus flavus Induce M1 Polarization In Vitro

• Published in: mSphere 2020-05, Vol.5 (3)
• Main Authors: Brauer, Verônica S, Pessoni, André M, Bitencourt, Tamires A, de Paula, Renato G, de Oliveira Rocha, Liliana, Goldman, Gustavo H, Almeida, Fausto
• Format: Article
• Language: English
• Subjects: Aspergillosis; Aspergillus flavus; Biological activity; Bone marrow; Cytokines; Experiments; Extracellular vesicles; Food contamination; Fungal infections; Fungi; Galleria mellonella; Genotype & phenotype; Host-Microbe Biology; IL-1β; Immune system; Immunocompromised hosts; Immunomodulation; Inflammation; Innate immunity; Inoculation; Interleukin 6; Larvae; Macrophages; Morbidity; Nanoparticles; Nitric oxide; Phagocytosis; Polarization; Tumor necrosis factor-TNF; Tumor necrosis factor-α; Virulence factors
• ISSN: 2379-5042; 2379-5042
• DOI: 10.1128/mSphere.00190-20

, 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 EVs and their immunomodulatory functions. We verified that 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 EVs enhance phagocytosis and killing by macrophages and induce M1 macrophage polarization In addition, a prior inoculation of EVs in larvae resulted in a protective effect against the fungal infection. Our findings suggest that EVs are biologically active and affect the interaction between and host immune cells, priming the innate immune system to eliminate the fungal infection. Collectively, our results suggest that EVs play a crucial role in aspergillosis. Immunocompromised patients are susceptible to several fungal infections. The genus 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 , a fungus considered to be the second most common cause of aspergillosis and relevant food contaminator found worldwide. In this study, we produced EVs and evaluated the immunomodulatory effects of EVs on bone marrow-derived macrophages (BMDMs) and effects in a model.