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鼠李糖乳杆菌后生元诱导的免疫调节作用作为使用活菌的更安全替代方法。

Lactobacillus rhamnosus postbiotic-induced immunomodulation as safer alternative to the use of live bacteria.

机构信息

Cell Biology Unit, Institut Pasteur de Montevideo, Montevideo, Uruguay; Laboratory of Immunobiotechnology, Reference Centre for Lactobacilli (CERELA-CONICET), San Miguel de Tucumán, Tucumán, Argentina.

Cell Biology Unit, Institut Pasteur de Montevideo, Montevideo, Uruguay; Laboratorio de Biotecnología, Facultad de Ingeniería-Universidad ORT Uruguay, Cuareim 1451, 11100 Montevideo, Uruguay.

出版信息

Cytokine. 2021 Oct;146:155631. doi: 10.1016/j.cyto.2021.155631. Epub 2021 Jul 10.

Abstract

Many attempts have been made to search for safer immunomodulatory agents that enhance the immune response and reduce the number and severity of infections in at-risk populations. The use of postbiotics, non-viable microbial cells or cell fractions that confer a health benefit to the consumer, represents a safe and attractive way to modulate and enhance the immune function in order to improve human health. Therefore, the aim of this work is to evaluate the immunoregulatory effect of Lactobacillus rhamnosus CRL1505 postbiotics in a complex culture system using human intestinal epithelial cells (IECs) and dendritic cells (DCs) differentiated from peripheral blood mononuclear cells. First, we demonstrated that L. rhamnosus CRL1505 differentially modulate human IECs and DCs after the challenge with the TLR4 agonist LPS. The CRL1505 strain down-regulated CD40, CD80 and CD86 expression in DCs, and increased their production of TNF-α, IL-1β, IL-6 and IL-10. Interestingly, the non-viable strain was able to modulate the immune response of both types of human cells. Then, we showed that cell wall (CW1505) and peptidoglycan (PG1505) from L. rhamnosus CRL1505 modulated TLR4-triggered immune response in IECs and DCs. Of interest, CW1505 showed a strong stimulatory effect while the PG1505 presented immune characteristics that were more similar to viable and non-viable CRL1505. To date, several molecules of immunobiotics were identified, that can be connected to specific host-responses. We hereby demonstrated that peptidoglycan of L. rhamnosus CRL1505 is a key molecule for the immunobiotic properties of this strain in human IECs and DCs. Likewise, the result of these studies could provide predictive tools for the in vivo efficacy of postbiotics and the scientific basis for their future applications in immunocompromised patients.

摘要

已经有许多尝试旨在寻找更安全的免疫调节剂,以增强免疫反应并减少高危人群中感染的数量和严重程度。使用后生元,即对消费者有益的非存活微生物细胞或细胞部分,是一种安全且有吸引力的调节和增强免疫功能的方法,以改善人类健康。因此,本工作的目的是在使用来自外周血单核细胞分化的人肠道上皮细胞(IEC)和树突状细胞(DC)的复杂培养系统中评估鼠李糖乳杆菌 CRL1505 后生元的免疫调节作用。首先,我们证明在 TLR4 激动剂 LPS 刺激后,鼠李糖乳杆菌 CRL1505 可差异调节人 IEC 和 DC。该菌株下调 DC 中 CD40、CD80 和 CD86 的表达,并增加其 TNF-α、IL-1β、IL-6 和 IL-10 的产生。有趣的是,非存活菌株能够调节两种类型的人细胞的免疫反应。然后,我们表明,来自鼠李糖乳杆菌 CRL1505 的细胞壁(CW1505)和肽聚糖(PG1505)调节 TLR4 触发的 IEC 和 DC 的免疫反应。有趣的是,CW1505 表现出强烈的刺激作用,而 PG1505 呈现出更类似于存活和非存活 CRL1505 的免疫特征。迄今为止,已经鉴定出几种免疫生物的分子,这些分子可以与特定的宿主反应相关联。我们在此证明,鼠李糖乳杆菌 CRL1505 的肽聚糖是该菌株在人 IEC 和 DC 中具有免疫生物特性的关键分子。同样,这些研究的结果可以为后生元在体内功效提供预测工具,并为它们在免疫功能低下患者中的未来应用提供科学依据。

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