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基于微粒的检测方法确定激动剂密度还是激动剂数量对免疫激活更重要。

Determining Whether Agonist Density or Agonist Number Is More Important for Immune Activation via Micoparticle Based Assay.

机构信息

Pritzker School of Molecular Engineering, The University of Chicago, Chicago, IL, United States.

出版信息

Front Immunol. 2020 Apr 9;11:642. doi: 10.3389/fimmu.2020.00642. eCollection 2020.

DOI:10.3389/fimmu.2020.00642
PMID:32328073
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7161694/
Abstract

It is unknown if surface bound toll-like-receptor (TLR) agonists activate cells via density or total molecular number. To answer this question, we developed a TLR agonist surface conjugated polystyrene microparticle (MP) system. Using a library of MPs with varying TLR agonist density and number, we simultaneously observed innate immune cell MP uptake and TNFα expression using ImageStream flow cytometry on a cell by cell basis. The data shows that total TLR number and not density drives cellular activation with a threshold of approximately 10-10 TLR agonists. We believe that this information will be crucial for the design of particulate vaccine formulations.

摘要

目前尚不清楚表面结合的 Toll 样受体 (TLR) 激动剂是通过密度还是总分子数来激活细胞。为了解决这个问题,我们开发了一种 TLR 激动剂表面结合的聚苯乙烯微球 (MP) 系统。使用具有不同 TLR 激动剂密度和数量的 MP 文库,我们在单细胞基础上使用 ImageStream 流式细胞术同时观察固有免疫细胞对 MP 的摄取和 TNFα 的表达。数据表明,总 TLR 数量而不是密度驱动细胞激活,其阈值约为 10-10 TLR 激动剂。我们相信,这些信息对于颗粒状疫苗制剂的设计至关重要。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d628/7161694/7ad89845c690/fimmu-11-00642-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d628/7161694/518c38d917e1/fimmu-11-00642-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d628/7161694/e1e191af120d/fimmu-11-00642-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d628/7161694/7ad89845c690/fimmu-11-00642-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d628/7161694/518c38d917e1/fimmu-11-00642-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d628/7161694/e1e191af120d/fimmu-11-00642-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d628/7161694/7ad89845c690/fimmu-11-00642-g003.jpg

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Co-delivery of Dual Toll-Like Receptor Agonists and Antigen in Poly(Lactic-Co-Glycolic) Acid/Polyethylenimine Cationic Hybrid Nanoparticles Promote Efficient Immune Responses.聚(乳酸-共-乙醇酸)/聚乙烯亚胺阳离子杂化纳米颗粒中双重Toll样受体激动剂与抗原的共递送促进高效免疫反应
Front Immunol. 2017 Sep 13;8:1077. doi: 10.3389/fimmu.2017.01077. eCollection 2017.
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Surface Coating of Nanoparticles Reduces Background Inflammatory Activity while Increasing Particle Uptake and Delivery.
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ACS Biomater Sci Eng. 2017 Feb 13;3(2):206-213. doi: 10.1021/acsbiomaterials.6b00473. Epub 2016 Dec 1.
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Combinatorial Delivery of Dual and Triple TLR Agonists via Polymeric Pathogen-like Particles Synergistically Enhances Innate and Adaptive Immune Responses.聚合物类病原体样颗粒协同递呈双重和三重 TLR 激动剂可显著增强固有和适应性免疫应答。
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