Exit of Mycobacterium avium from granuloma macrophages
鸟分枝杆菌从肉芽肿巨噬细胞中退出
基本信息
- 批准号:446317895
- 负责人:
- 金额:--
- 依托单位:
- 依托单位国家:德国
- 项目类别:Priority Programmes
- 财政年份:2021
- 资助国家:德国
- 起止时间:2020-12-31 至 2023-12-31
- 项目状态:已结题
- 来源:
- 关键词:
项目摘要
Non-tuberculous mycobacteria are common inhabitants in the environment of children. Mycobacterium avium is the most frequently isolated non-tuberculous mycobacterial species in chronic tissue infections in infants and toddlers. From school age onwards, M. avium infections usually affect people with underlying diseases, e.g. immunodeficiency syndromes or chronic lung disease. M. avium predominantly infects macrophages (Mac), which contribute, as defined species like giant and epitheloid cells, to organized tissue reactions called granulomas. The development of granulomas with respect to resident and incoming immune cells, as well as mycobacteria infecting individual cells, is highly dynamic and crucial for both mycobacterial containment and immune mediated pathology. In this proposal, mechanisms of M. avium exit from defined Mac and progenitor species both in vitro and in mouse infection models will be analyzed, in order to test the following model: M. avium exits primarily infected resident tissue Macs by driving them into apoptosis. Apoptotic Mac are the taken up by incoming Mac progenitors transforming into giant cells. This allows for granuloma growth/maturation, and local M. avium persistence. Specific foci will lie on dissecting M. avium-induced cell death, in particular apoptosis, as a key exit mechanism, which mycobacteria use to subvert Mac immunity, for intercellular bacterial transfer and to drive formation of relatively permissive granulomas. Another focus will be on how the Mac origin and differentiation state, i.e. acutely bone marrow-derived and progenitor like, versus or tissue resident fully site adapted, determine exit pathways, as well as mycobacterial adaptation for the intracellular environment. To achieve these goals, we will combine in vitro models with fate mapping, transcriptome analysis, high resolution imaging and adoptive cell transfer.
非结核分枝杆菌是儿童环境中常见的居民。鸟分枝杆菌是婴幼儿慢性组织感染中最常见的非结核分枝杆菌。从学龄起,鸟支原体感染通常影响患有基础疾病的人,例如免疫缺陷综合征或慢性肺病。鸟分枝杆菌主要感染巨噬细胞(Mac),巨噬细胞作为巨细胞和上皮细胞等定义的物种,有助于组织反应,称为肉芽肿。肉芽肿的发展与常驻和传入的免疫细胞有关,以及分枝杆菌感染单个细胞,是高度动态的,对分枝杆菌控制和免疫介导的病理都至关重要。在本研究中,我们将在体外和小鼠感染模型中分析禽分枝杆菌从定义的Mac和祖物种中退出的机制,以验证以下模型:禽分枝杆菌主要通过驱动被感染的常驻组织Mac细胞凋亡而退出。凋亡的Mac被进入的Mac祖细胞吸收,转化为巨细胞。这允许肉芽肿生长/成熟,和局部的鸟分枝杆菌持续存在。具体的重点将放在解剖M. avium诱导的细胞死亡,特别是细胞凋亡,作为一个关键的退出机制,分枝杆菌利用它来破坏Mac免疫,细胞间细菌转移和驱动形成相对允许的肉芽肿。另一个重点将是Mac的起源和分化状态,即急性骨髓源性和祖细胞样,与完全适应于原位的组织相比,如何决定退出途径,以及分枝杆菌对细胞内环境的适应。为了实现这些目标,我们将结合体外模型与命运图谱、转录组分析、高分辨率成像和过继细胞转移。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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Professor Dr. Philipp Henneke其他文献
Professor Dr. Philipp Henneke的其他文献
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{{ truncateString('Professor Dr. Philipp Henneke', 18)}}的其他基金
Macrophage differentiation in staphylococcal skin infection
葡萄球菌皮肤感染中的巨噬细胞分化
- 批准号:
283781347 - 财政年份:2015
- 资助金额:
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Research Grants
TLR-dependent formation of multinucleated giant cells
TLR依赖性多核巨细胞的形成
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254895677 - 财政年份:2014
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-- - 项目类别:
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Molecular definition of a novel phagolysosomal receptor for streptococcal RNA
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202719428 - 财政年份:2011
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Die Rolle des Insulinrezeptors in der angeborenen Immunantwort gegen Gruppe B Streptokokken
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33421478 - 财政年份:2007
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Clustering and activation of a macrophage receptor for Streptococcus agalactiae
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5401456 - 财政年份:2003
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Molekulare Mechanismen der Zellaktivierung durch Streptokokken der Gruppe-B - die Rolle der Membran-Rezeptoren CD14 und CR3 für Signaltransduktion und Zytokinsynthese
B 族链球菌细胞活化的分子机制 - 膜受体 CD14 和 CR3 在信号转导和细胞因子合成中的作用
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5183648 - 财政年份:1999
- 资助金额:
-- - 项目类别:
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