Bacterial extracellular vesicles as intranasal postbiotics: Detailed characterization and interaction with airway cells

IF 15.5 1区 医学 Q1 CELL BIOLOGY Journal of Extracellular Vesicles Pub Date : 2024-10-21 DOI:10.1002/jev2.70004
Agnieszka Razim, Agnieszka Zabłocka, Anna Schmid, Michael Thaler, Viktor Černý, Tamara Weinmayer, Bradley Whitehead, Anke Martens, Magdalena Skalska, Mattia Morandi, Katy Schmidt, Magdalena E. Wysmołek, Akos Végvári, Dagmar Srutkova, Martin Schwarzer, Lukas Neuninger, Peter Nejsum, Jiri Hrdý, Johan Palmfeldt, Marco Brucale, Francesco Valle, Sabina Górska, Lukas Wisgrill, Aleksandra Inic-Kanada, Ursula Wiedermann, Irma Schabussova
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Abstract

Escherichia coli A0 34/86 (EcO83) is a probiotic strain used in newborns to prevent nosocomial infections and diarrhoea. This bacterium stimulates both pro- and anti-inflammatory cytokine production and its intranasal administration reduces allergic airway inflammation in mice. Despite its benefits, there are concerns about the use of live probiotic bacteria due to potential systemic infections and gene transfer. Extracellular vesicles (EVs) derived from EcO83 (EcO83-EVs) might offer a safer alternative to live bacteria. This study characterizes EcO83-EVs and investigates their interaction with host cells, highlighting their potential as postbiotic therapeutics. EcO83-EVs were isolated, purified, and characterised following the Minimal Information of Studies of Extracellular Vesicles (MISEV) guidelines. Ex vivo studies conducted in human nasal epithelial cells showed that EcO83-EVs increased the expression of proteins linked to oxidative stress and inflammation, indicating an effective interaction between EVs and the host cells. Further in vivo studies in mice demonstrated that EcO83-EVs interact with nasal-associated lymphoid tissue, are internalised by airway macrophages, and stimulate neutrophil recruitment in the lung. Mechanistically, EcO83-EVs activate the NF-κΒ signalling pathway, resulting in the nitric oxide production. EcO83-EVs demonstrate significant potential as a postbiotic alternative to live bacteria, offering a safer option for therapeutic applications. Further research is required to explore their clinical use, particularly in mucosal vaccination and targeted immunotherapy strategies.

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作为鼻内后生物制剂的细菌胞外囊泡:详细表征及与气道细胞的相互作用
大肠杆菌 A0 34/86(EcO83)是一种益生菌株,用于新生儿预防院内感染和腹泻。这种细菌既能刺激促炎细胞因子的产生,也能刺激抗炎细胞因子的产生,鼻内给药能减轻小鼠过敏性气道炎症。尽管益生菌有很多益处,但由于其潜在的全身感染和基因转移问题,人们对使用活益生菌仍有顾虑。从 EcO83 提取的胞外囊泡 (EVs)(EcO83-EVs)可能是活菌更安全的替代品。本研究描述了 EcO83-EVs 的特征,并研究了它们与宿主细胞的相互作用,突出了它们作为后生物疗法的潜力。EcO83-EVs是按照细胞外囊泡研究的最低信息量(MISEV)指南进行分离、纯化和表征的。在人鼻上皮细胞中进行的体内外研究表明,EcO83-EVs 增加了与氧化应激和炎症有关的蛋白质的表达,这表明 EVs 与宿主细胞之间存在有效的相互作用。在小鼠体内进行的进一步研究表明,EcO83-EV 与鼻腔相关淋巴组织相互作用,被气道巨噬细胞内化,并刺激肺部中性粒细胞的募集。从机理上讲,EcO83-EVs 可激活 NF-κΒ 信号通路,从而产生一氧化氮。EcO83-EVs作为活菌的后生物替代品具有巨大潜力,为治疗应用提供了更安全的选择。要探索其临床应用,特别是在粘膜疫苗接种和靶向免疫疗法策略中的应用,还需要进一步的研究。
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来源期刊
Journal of Extracellular Vesicles
Journal of Extracellular Vesicles Biochemistry, Genetics and Molecular Biology-Cell Biology
CiteScore
27.30
自引率
4.40%
发文量
115
审稿时长
12 weeks
期刊介绍: The Journal of Extracellular Vesicles is an open access research publication that focuses on extracellular vesicles, including microvesicles, exosomes, ectosomes, and apoptotic bodies. It serves as the official journal of the International Society for Extracellular Vesicles and aims to facilitate the exchange of data, ideas, and information pertaining to the chemistry, biology, and applications of extracellular vesicles. The journal covers various aspects such as the cellular and molecular mechanisms of extracellular vesicles biogenesis, technological advancements in their isolation, quantification, and characterization, the role and function of extracellular vesicles in biology, stem cell-derived extracellular vesicles and their biology, as well as the application of extracellular vesicles for pharmacological, immunological, or genetic therapies. The Journal of Extracellular Vesicles is widely recognized and indexed by numerous services, including Biological Abstracts, BIOSIS Previews, Chemical Abstracts Service (CAS), Current Contents/Life Sciences, Directory of Open Access Journals (DOAJ), Journal Citation Reports/Science Edition, Google Scholar, ProQuest Natural Science Collection, ProQuest SciTech Collection, SciTech Premium Collection, PubMed Central/PubMed, Science Citation Index Expanded, ScienceOpen, and Scopus.
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