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生成三维人体肉芽肿以研究宿主相互作用。

Generating Three-dimensional Human Granulomas to Study -Host Interaction.

作者信息

Arbués Ainhoa, Kammüller Michael, Portevin Damien

机构信息

Department of Medical Parasitology and Infection Biology, Swiss Tropical and Public Health Institute, Basel, Switzerland.

University of Basel, Basel, Switzerland.

出版信息

Bio Protoc. 2020 Nov 20;10(22):e3820. doi: 10.21769/BioProtoc.3820.

DOI:10.21769/BioProtoc.3820
PMID:33659472
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7842406/
Abstract

Granulomas are organized multicellular structures that constitute the hallmark of an infection by the human pathogen A better understanding of the complex host- interactions within the granuloma's environment may lead to new therapeutic or preventive tools to improve the control of the tuberculosis pandemic. To date, several models that are able to mimic human nascent granulomas have been reported. Here we describe a protocol in which -infected human peripheral blood mononuclear cells (PBMCs) are embedded within a collagen matrix leading to the formation of three-dimensional micro-granulomas. Subsequently, PBMCs and can be retrieved allowing multiparametric readouts from both the host and the pathogen. In addition to the incorporation of a physiological extracellular matrix, this model has the singular advantage of recapitulating dormant-like features, as well as reproducing resuscitation observed under immunomodulatory treatments, which have not been reported in other published protocols to generate granulomas.

摘要

肉芽肿是有组织的多细胞结构,是人类病原体感染的标志。更好地理解肉芽肿环境中复杂的宿主相互作用,可能会带来新的治疗或预防手段,以改善对结核病大流行的控制。迄今为止,已经报道了几种能够模拟人类新生肉芽肿的模型。在此,我们描述一种方案,即将感染的人类外周血单核细胞(PBMC)嵌入胶原蛋白基质中,从而形成三维微肉芽肿。随后,可以获取PBMC和病原体,以便对宿主和病原体进行多参数读数。除了包含生理细胞外基质外,该模型具有独特的优势,即能够重现类似休眠的特征,以及再现免疫调节治疗下观察到的复苏情况,而在其他已发表的生成肉芽肿的方案中尚未报道过这些情况。

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PLoS Pathog. 2020 Feb 18;16(2):e1008312. doi: 10.1371/journal.ppat.1008312. eCollection 2020 Feb.
2
The Immune Mechanisms of Lung Parenchymal Damage in Tuberculosis and the Role of Host-Directed Therapy.肺结核中肺实质损伤的免疫机制及宿主导向治疗的作用
Front Microbiol. 2018 Oct 30;9:2603. doi: 10.3389/fmicb.2018.02603. eCollection 2018.
3
Functional characterization and phenotypic monitoring of human hematopoietic stem cell expansion and differentiation of monocytes and macrophages by whole-cell mass spectrometry.通过全细胞质谱法对人造血干细胞扩增以及单核细胞和巨噬细胞分化进行功能表征和表型监测。
Stem Cell Res. 2018 Jan;26:47-54. doi: 10.1016/j.scr.2017.11.013. Epub 2017 Nov 22.
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Dissection of the host-pathogen interaction in human tuberculosis using a bioengineered 3-dimensional model.使用生物工程三维模型剖析人类结核病中的宿主-病原体相互作用。
Elife. 2017 Jan 7;6:e21283. doi: 10.7554/eLife.21283.
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Dissecting host factors that regulate the early stages of tuberculosis infection.剖析调控结核病感染早期阶段的宿主因素。
Tuberculosis (Edinb). 2016 Sep;100:102-113. doi: 10.1016/j.tube.2016.07.009. Epub 2016 Jul 25.
6
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7
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8
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