Cellular and transcriptomic analysis of regulatory T cells in streptococcal infection

链球菌感染中调节性 T 细胞的细胞和转录组分析

• 批准号: G0901386/1
• 负责人: Daniel Altmann
• 金额: $ 19.67万
• 依托单位: Imperial College London
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2010
• 资助国家: 英国
• 起止时间: 2010 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=G0901386%2F1
• 关键词: Cellular; transcriptomic; analysis; regulatory; cells

This proposal is concerned with a population of white blood cells termed ?regulatory T cells? (Tregs). Their role in the body is to damp down other immune cells, preventing inflammatory ?overshoot?. We wish to examine what they do in a particular setting of bacterial infection: infections with Streptococcus pyogenes cause diverse conditions from sore throat to scarlet fever, rheumatic heart disease, sepsis and necrotising fasciitis (?flesh-eating disease?). We know that the interplay between the body and this bacterium is a complex one: on the one hand, a robust immune response is required to defend the body, while on the other, many of the disease manifestations are themselves a consequence of over-exuberant immunity. It is immediately apparent that there is likely to be an important role of Tregs. The Altmann lab has already shown (in mouse models) that there is a very rapid up-regulation of Tregs and molecules associated with them at the site of infection with this bacterium. The aim of this new proposal is to start building up an understanding of what happens in human cells. The proposal brings together investigators with highly complementary interests in this area in Singapore and London ? Altmann (Imperial) has been interested in models of streptococcal sepsis and the role of Tregs, Rotzschke (SiGN) has been involved in the detailed cellular and molecular analysis of Tregs, and Yang (SiGN) uses DNA microarray technology to describe immune responses. This latter approach is a very powerful one, allowing comparative analysis of cells that have been treated in different ways by looking at tens of thousands of human genes and asking, in a particular situation, which genes are turned up and which turned down. The 3 teams will build a close collaboration through annual workshops, monthly videoconferences, and by sending personnel between labs to work together. The central group of experiments depend on culturing cells from human tonsils, either in the presence or absence of Tregs, then infecting the cultures with various versions of Strep, of varying virulence. We will compare what happens, with or without Tregs, in terms of the presence of specific cell populations and gene by gene, though array anaysis. We will back up these human studies with experiments whereby we give the Strep to mice that either have normal Tregs, or have had them genetically knocked out. These experiments should lead to an improved understanding of the immunological events controlling these diseases.

这个建议是关于一群白色血细胞，称为？调节性T细胞（Tennis）.它们在体内的作用是抑制其他免疫细胞，防止炎症？过冲？我们希望研究它们在细菌感染的特定环境中的作用：化脓性链球菌感染引起从喉咙痛到猩红热、风湿性心脏病、脓毒症和坏死性筋膜炎的各种疾病（？食腐病？）。我们知道身体和这种细菌之间的相互作用是复杂的：一方面，需要强大的免疫反应来保护身体，而另一方面，许多疾病的表现本身就是免疫力过度旺盛的结果。很明显，可能会有一个重要的作用，Tibetan。Altmann实验室已经证明（在小鼠模型中），在感染这种细菌的部位，Tibetin及其相关分子的表达非常迅速。这项新提议的目的是开始建立对人类细胞中发生的事情的理解。该提案将新加坡和伦敦在这一领域具有高度互补利益的调查人员聚集在一起？Altmann（Imperial）一直对链球菌败血症模型和THBG的作用感兴趣，Rotzschke（SiGN）参与了THBG的详细细胞和分子分析，Yang（SiGN）使用DNA微阵列技术描述免疫反应。后一种方法非常强大，它可以通过观察成千上万的人类基因，并在特定情况下询问哪些基因被激活，哪些基因被关闭，来对以不同方式处理的细胞进行比较分析。这三个团队将通过年度研讨会、每月视频会议以及在实验室之间派遣人员共同工作来建立密切的合作关系。实验的核心组是在有或没有Tclase的情况下培养人扁桃体细胞，然后用不同毒力的各种版本的链球菌感染培养物。我们将通过阵列分析，在特定细胞群和基因的存在方面，比较有或没有TdR的情况。我们将通过实验来支持这些人类研究，我们将链球菌给予具有正常THP或基因敲除的小鼠。这些实验应该导致控制这些疾病的免疫学事件的更好的理解。