在小鼠骨髓树突状细胞中,灭活的副疱疹病毒(iPPVO)对TLR9的依赖性激活与特定毒株依赖性树突状细胞亚群有关。

IF 4.7 3区 医学 Q2 IMMUNOLOGY
Journal of Innate Immunity Pub Date : 2024-01-01 Epub Date: 2024-06-08 DOI:10.1159/000538625
Yanqin Du, Hang Sun, Sonakshi Bhattacharjee, Alexander Birkmann, Ulf Dittmer, Mengji Lu
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引用次数: 0

摘要

简介灭活的副疱疹病毒(iPPVO)对先天性免疫细胞有很强的免疫调节作用,因此是一种很有吸引力的候选疗法。然而,人们对参与 iPPVO 诱导免疫反应的信号通路知之甚少:在这项研究中,我们通过流式细胞术和酶联免疫吸附试验系统分析了不同类型的树突状细胞(DCs)如何对 BALB/c 和 C57BL/c 小鼠的 iPPVO(Zylexis,D1710 株)产生反应,并通过 Western 印迹和蛋白质谱分析研究了与 DC 活化相关的信号通路:结果:我们发现骨髓来源的常规DC(BM-cDCs)和骨髓来源的浆细胞DC(BM-pDCs)在Zylexis的刺激下成熟并分泌IFN-α/β。同样,Zylexis 可促进 pDCs 分泌 IL-12/23p40 和 TNF。然而,BALB/c小鼠能诱导cDCs分泌IL-12/23p40和TNF,而C57BL/6小鼠则不能。对潜在信号通路的分析表明,iPPVO 诱导的 cDCs 成熟与 TLR9 无关,而 pDCs 的成熟部分依赖于 TLR9 通路。此外,在两种小鼠品系中,cDCs 产生促炎细胞因子和 pDCs 分泌 IFN-α/β 部分依赖于 TLR9 通路。因此,其他信号通路似乎也参与了 DCs 对 iPPVO 的反应,蛋白质谱分析也证实了这一点:我们的数据为了解 iPPVO 传感器的多样性及其对不同品系和物种的不同影响提供了有用的见解。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
TLR9-Dependent Activation by Inactivated Parapoxvirus Ovis in Murine Bone Marrow-Derived Dendritic Cells Is Associated with Specific Strain-Dependent Dendritic Cell Subsets.

Introduction: Inactivated parapoxvirus ovis (iPPVO) exerts strong immunomodulatory effects on innate immune cells, making it an attractive therapeutic candidate. However, little is known about the signaling pathways that are involved in iPPVO-induced immune responses.

Methods: In this study, we systematically analyzed how different types of dendritic cells (DCs) react to iPPVO (Zylexis, strain D1701) in both BALB/c and C57BL/6 mice by flow cytometry and ELISAs, and investigated which signaling pathway is related to DC activation by Western blotting and protein profiling.

Results: We demonstrated that bone marrow-derived conventional DCs (BM-cDCs) and bone marrow-derived plasmacytoid DCs (BM-pDCs) matured and secreted type I interferons in response to Zylexis stimulation in both mouse strains. Similarly, Zylexis promoted the secretion of IL-12/23p40 and TNF by pDCs. However, IL-12/23p40 and TNF secretion by cDCs were induced in BALB/c mice but not in C57BL/6 mice. Analyzing the underlying signaling pathways revealed that iPPVO-induced maturation of cDCs was Toll-like receptor 9 (TLR9) independent, while the maturation of pDCs partially depended on the TLR9 pathway. Moreover, the production of proinflammatory cytokines by cDCs and the secretion of IFN-α/β by pDCs partially depended on the TLR9 pathway in both mouse strains. Therefore, other signaling pathways seem to participate in the response of DCs to iPPVO, supported by protein profiling.

Conclusion: Our data provide useful insights into the diversity of iPPVO sensors and their varying effects across different strains and species.

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来源期刊
Journal of Innate Immunity
Journal of Innate Immunity 医学-免疫学
CiteScore
10.50
自引率
1.90%
发文量
35
审稿时长
7.5 months
期刊介绍: The ''Journal of Innate Immunity'' is a bimonthly journal covering all aspects within the area of innate immunity, including evolution of the immune system, molecular biology of cells involved in innate immunity, pattern recognition and signals of ‘danger’, microbial corruption, host response and inflammation, mucosal immunity, complement and coagulation, sepsis and septic shock, molecular genomics, and development of immunotherapies. The journal publishes original research articles, short communications, reviews, commentaries and letters to the editors. In addition to regular papers, some issues feature a special section with a thematic focus.
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