Single cell approach to study host/enteric virus interaction in human mini-gut organoids

单细胞方法研究人类小肠类器官中宿主/肠道病毒相互作用

• 批准号: 416072091
• 负责人: Dr. Megan Stanifer, Ph.D.
• 金额: --
• 依托单位: University of South Florida (USF)
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2019
• 资助国家: 德国
• 起止时间: 2018-12-31 至 2020-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/416072091?language=en
• 关键词: Single; cell; approach; study; host

Characterization of host/enteric pathogens interactions using immortalized intestinal epithelial cell lines do not reflect the complex environment that both the pathogens and the cellular intrinsic immune system face in the human gut. Indeed, the intestinal tract is characterized by the presence of multiple specific cell lineages arranged within a crypt/villi axis, which must tolerate the commensal flora but be primed for enteric virus attacks. In this proposal, we will exploit both single cell transcriptomic analyses and visualization of immune response in live mini-gut organoids during enteric virus infection. We will characterize the intrinsic innate immune response of intestinal epithelial cells in the context of the intestinal epithelium organization. This will allow us to describe, at the single cell level, the antiviral innate immune response generated by each individual cell type naturally present in the human gut and to characterize how both infection and immune response spread in space and time within the crypt/villi axis organized gut epithelium. At the completion of this project we will have developed a physiological culture system allowing us to address the complex interplay between pathogen/epithelial cells. This will offer us unprecedented perspectives to study host/pathogen interactions and intestinal disease.

使用永生化肠上皮细胞系表征宿主/肠道病原体相互作用不能反映病原体和细胞内在免疫系统在人肠道中面临的复杂环境。事实上，肠道的特征在于存在排列在隐窝/绒毛轴内的多个特异性细胞谱系，其必须耐受肠道植物群，但为肠道病毒攻击做好准备。在这项提案中，我们将利用单细胞转录组学分析和肠道病毒感染期间活的小肠道类器官中免疫反应的可视化。我们将描述肠上皮组织背景下肠上皮细胞的内在先天免疫反应。这将使我们能够在单细胞水平上描述由天然存在于人肠道中的每种细胞类型产生的抗病毒先天免疫应答，并表征感染和免疫应答如何在隐窝/绒毛轴组织的肠道上皮内在空间和时间上传播。在这个项目完成后，我们将开发一个生理培养系统，使我们能够解决病原体/上皮细胞之间复杂的相互作用。这将为我们研究宿主/病原体相互作用和肠道疾病提供前所未有的视角。