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IL-10+ B细胞的激活:治疗性细菌悬液的一种新型免疫调节机制。

Activation of IL-10+ B cells: A novel immunomodulatory mechanism for therapeutic bacterial suspensions.

作者信息

Salazar Alberto, Nieto Jane E, Velazquez-Soto Henry, Jiménez-Martínez Maria C

机构信息

Department of Biochemistry, Faculty of Medicine, National Autonomous University of Mexico, Mexico City, Mexico.

Department of Immunology and Research Unit, Institute of Ophthalmology "Conde de Valenciana," Mexico City, Mexico.

出版信息

SAGE Open Med. 2020 Jan 15;8:2050312120901547. doi: 10.1177/2050312120901547. eCollection 2020.

Abstract

OBJECTIVES

Bacterial components are used to improve immune responses in patients with respiratory infections. Pharmacological formulations of bacterial components include a mixture of bacterial antigens, some of which are complete inactivated bacteria, that is, named bacterial suspensions; while others are fragments of bacteria, which are presented as bacterial lysates. Although bacterial lysates have been broadly used as immune-stimulators, the biological support for the therapeutic effectiveness of bacterial suspension has not yet been studied. Thus, the aim of our study was to investigate the immunological activity induced by bacterial suspension.

METHODS

This work was an exploratory translational study. Peripheral blood mononuclear cells were obtained from healthy donors and cultured in time-dose dependent assays with a commercial bacterial suspension. Flow cytometry was used for phenotypic analysis and for determining soluble cytokines in culture supernatants.

RESULTS

We observed that bacterial suspension activates B cells in a dose-dependent manner. Peripheral blood mononuclear cells were able to secrete IL-6 and IL-10 after 24 h of bacterial suspension stimulation. TLR2 expression was observed mainly on CD19+ CD38 B cells after 72 h of culture; remarkably, most of the TLR2+ CD19+ cells were also IL-10+.

CONCLUSION

Our findings suggest that bacterial suspension induces the activation of B cell subsets as well as the secretion of IL-6 and IL-10. Expression of TLR2 on CD19+ cells could act as an activation loop of IL-10+ B regulatory cells. The clinical implications of these findings are discussed at the end of this article.

摘要

目的

细菌成分被用于改善呼吸道感染患者的免疫反应。细菌成分的药理学制剂包括细菌抗原混合物,其中一些是完全灭活的细菌,即所谓的细菌悬液;而其他的是细菌片段,以细菌裂解物的形式呈现。尽管细菌裂解物已被广泛用作免疫刺激剂,但细菌悬液治疗效果的生物学依据尚未得到研究。因此,我们研究的目的是调查细菌悬液诱导的免疫活性。

方法

这项工作是一项探索性转化研究。从健康供体获取外周血单个核细胞,并与一种商业细菌悬液进行时间-剂量依赖性分析培养。流式细胞术用于表型分析和测定培养上清液中的可溶性细胞因子。

结果

我们观察到细菌悬液以剂量依赖性方式激活B细胞。细菌悬液刺激24小时后,外周血单个核细胞能够分泌IL-6和IL-10。培养72小时后,TLR2表达主要在CD19+ CD38 B细胞上观察到;值得注意的是,大多数TLR2+ CD19+细胞也是IL-10+。

结论

我们的研究结果表明,细菌悬液诱导B细胞亚群的激活以及IL-6和IL-10的分泌。CD19+细胞上TLR2的表达可能作为IL-10+ B调节细胞的激活环。本文结尾讨论了这些发现的临床意义。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a1d3/6963315/5de69c48c092/10.1177_2050312120901547-fig1.jpg

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