Role of Innate lymphoid cells (ILC) and aryl hydrocarbon receptor (AhR) during pulmonary bacterial infections
先天淋巴细胞 (ILC) 和芳烃受体 (AhR) 在肺部细菌感染过程中的作用
基本信息
- 批准号:320429054
- 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:2016
- 资助国家:德国
- 起止时间:2015-12-31 至 2022-12-31
- 项目状态:已结题
- 来源:
- 关键词:
项目摘要
Pulmonary diseases caused by Pseudomonas aeruginosa (P.aer) represent one major cause of hospitalization and mortality, especially in immunocompromised individuals and in patients affected by cystic fibrosis. Intratracheal infection with P.aer can be used to study the acute immune response and inflammation, which is mainly mediated by the innate immune system, especially neutrophils, and spontaneously resolved within 96 h, together with complete bacterial clearance. IL-17 responses allegedly contribute to neutrophil recruitment and resistance against P.aer; however the sources of this cytokine as well as the role of lung innate lymphoid cells (ILCs) during P.aer infection remain unclear. S. Kaufmann (the Co-PI of this project during the first funding period) had shown that the aryl hydrocarbon receptor (AhR) acts as a recognition sensor for pigmented virulence factors from P.aer, and that impairment in AhR signalling affects bacterial load, host survival and tissue damage during in vivo infection. However, the immunological mechanisms responsible for this effect have only started to be elucidated. As AhR signalling is crucial in modulating differentiation and functions of T cells and ILCs, we aimed to investigate the role of AhR signalling and ILCs during P.aer infection.In the previous funding period, we have characterized ILC responses after in vivo intratracheal infection with P.aer and assessed the impact of conditional AhR deletion in different lymphocyte lineages. We could show that lung ILC3 and NKp46+ ILCs cells are both activated during in vivo infection with P.aer. However, while RORt-dependent lymphocytes, including ILC3, are dispensable for survival, selective deletion of AhR signalling in NKp46+ ILCs has a severe impact in the late survival and disease course after P.aer infection.Based on this data, we hypothesised that NKp46+ ILC may play a role in the late regulation of immunopathology, following P.aer infection. To test this hypothesis, in the next funding period, we aim to uncover the role of NKp46+ ILCs during P.aer infection and define the cell intrinsic signatures established by AhR signalling in these cells. This project will enable us unveiling the understudied role of ILCs during pulmonary bacterial infections and possibly help to identify new targets for the modulation of acute inflammation and tissue damage.
铜绿假单胞菌(P.aer)引起的肺部疾病是导致住院和死亡的主要原因之一,尤其是在免疫功能低下的人和囊性纤维化患者中。气管内感染P.aer可用于研究急性免疫反应和炎症反应,主要由天然免疫系统,特别是中性粒细胞介导,并在96h内自发消退,细菌完全清除。IL-17反应被认为有助于中性粒细胞的募集和对P.aer的抵抗;然而,这种细胞因子的来源以及肺固有淋巴样细胞(ILCs)在P.aer感染过程中的作用尚不清楚。S.Kaufmann(该项目在第一个资助期的Co-PI)的研究表明,芳烃受体(AhR)作为来自P.aer的色素毒力因子的识别传感器,AhR信号的障碍影响体内感染期间的细菌负荷、宿主存活和组织损伤。然而,导致这种效应的免疫学机制才刚刚开始阐明。由于AhR信号在调节T细胞和ILC的分化和功能中起关键作用,我们旨在研究AhR信号和ILC在P.aer感染过程中的作用。在之前的资助阶段,我们研究了P.aer体内感染后ILC的反应,并评估了条件性AhR缺失对不同淋巴细胞谱系的影响。我们可以证明,在体内感染P.aer时,肺ILC3和NKp46+ILCs细胞都被激活。然而,尽管包括ILC3在内的依赖于RoR的淋巴细胞对于生存是必不可少的,但选择性缺失NKp46+ILC中的AhR信号在P.aer感染后的晚期生存和疾病过程中具有严重的影响。为了验证这一假设,在下一个资金阶段,我们的目标是揭示NKp46+ILCs在P.aer感染过程中的作用,并定义这些细胞中AhR信号建立的细胞内在特征。这个项目将使我们能够揭示ILCs在肺部细菌感染中未被充分研究的作用,并可能有助于确定调节急性炎症和组织损伤的新靶点。
项目成果
期刊论文数量(0)
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Professorin Dr. Chiara Romagnani, Ph.D.其他文献
Professorin Dr. Chiara Romagnani, Ph.D.的其他文献
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{{ truncateString('Professorin Dr. Chiara Romagnani, Ph.D.', 18)}}的其他基金
Human intestinal innate lymphoid cells (ILCs): signatures and polarization signals
人肠道先天淋巴细胞 (ILC):特征和极化信号
- 批准号:
289483678 - 财政年份:2016
- 资助金额:
-- - 项目类别:
Research Grants
Innate mechanisms of chronic inflammation
慢性炎症的先天机制
- 批准号:
288867951 - 财政年份:2016
- 资助金额:
-- - 项目类别:
Heisenberg Professorships
Mechanisms of Natural Killer cell expansion and neoplastic transformation
自然杀伤细胞扩增和肿瘤转化的机制
- 批准号:
497784080 - 财政年份:
- 资助金额:
-- - 项目类别:
Research Grants
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Innate-likeB细胞受损介导凋亡细胞的清除障碍在系统性红斑狼疮发病中的作用及机制研究
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