Souza Jéssica Amanda Marques, Baltazar Ludmila de Matos, Carregal Virgínia Mendes, Gouveia-Eufrasio Ludmila, de Oliveira André Gustavo, Dias Wendell Girard, Campos Rocha Marina, Rocha de Miranda Kildare, Malavazi Iran, Santos Daniel de Assis, Frézard Frédéric Jean Georges, de Souza Daniele da Glória, Teixeira Mauro Martins, Soriani Frederico Marianetti
Centro de Pesquisa e Desenvolvimento de Fármacos, Departamento de Genética, Ecologia e Evolução, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil.
Laboratório de Interação Microrganismo-Hospedeiro, Departamento de Microbiologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil.
Front Microbiol. 2019 Sep 4;10:2008. doi: 10.3389/fmicb.2019.02008. eCollection 2019.
Extracellular vesicles (EVs) has been considered an alternative process for intercellular communication. EVs release by filamentous fungi and the role of vesicular secretion during fungus-host cells interaction remain unknown. Here, we identified the secretion of EVs from the pathogenic filamentous fungus, . Analysis of the structure of EVs demonstrated that produces round shaped bilayer structures ranging from 100 to 200 nm size, containing ergosterol and a myriad of proteins involved in REDOX, cell wall remodeling and metabolic functions of the fungus. We demonstrated that macrophages can phagocytose EVs. Phagocytic cells, stimulated with EVs, increased fungal clearance after conidia challenge. EVs were also able to induce the production of TNF-α and CCL2 by macrophages and a synergistic effect was observed in the production of these mediators when the cells were challenged with the conidia. In bone marrow-derived neutrophils (BMDN) treated with EVs, there was enhancement of the production of TNF-α and IL-1β in response to conidia. Together, our results demonstrate, for the first time, that produces EVs containing a diverse set of proteins involved in fungal physiology and virulence. Moreover, EVs are biologically active and stimulate production of inflammatory mediators and fungal clearance.
细胞外囊泡(EVs)已被认为是细胞间通讯的一种替代方式。丝状真菌释放的EVs以及囊泡分泌在真菌与宿主细胞相互作用中的作用仍不清楚。在此,我们鉴定了致病性丝状真菌 分泌的EVs。对EVs结构的分析表明, 产生的圆形双层结构大小在100至200纳米之间,含有麦角固醇和大量参与真菌氧化还原、细胞壁重塑及代谢功能的蛋白质。我们证明巨噬细胞可以吞噬 EVs。用EVs刺激吞噬细胞后,在分生孢子攻击后真菌清除率增加。EVs还能够诱导巨噬细胞产生TNF-α和CCL2,并且当细胞受到分生孢子攻击时,在这些介质的产生中观察到协同效应。在用EVs处理的骨髓来源的中性粒细胞(BMDN)中,对分生孢子的反应中TNF-α和IL-1β的产生增强。总之,我们的结果首次证明, 产生含有多种参与真菌生理学和毒力的蛋白质的EVs。此外,EVs具有生物活性,可刺激炎症介质的产生和真菌清除。