Studies on triggers and modulators of coccidia-induced NETosis: parasite glycans, ATP, AMPK, O2 and extracellular vesicles
球虫诱导的 NETosis 的触发因素和调节剂的研究:寄生虫聚糖、ATP、AMPK、O2 和细胞外囊泡
基本信息
- 批准号:216337519
- 负责人:
- 金额:--
- 依托单位:
- 依托单位国家:德国
- 项目类别:Research Grants
- 财政年份:
- 资助国家:德国
- 起止时间:
- 项目状态:未结题
- 来源:
- 关键词:
项目摘要
Infections with coccidian parasites, such as Besnoitia besnoiti or Eimeria bovis, considerably impair animal welfare and cause high economic losses in cattle industry. Overall, proper immune reactions play a key role in control of these parasitic infections. In our recent work, we identified several coccidian species and stages as potent triggers of “Neutrophil extracellular Trap” (NET) formation, which signifies an important effector mechanism of innate immune cells. The data of the preceding proposal show that the processes of NETosis and autophagy occur simultaneously in parasite-activated polymorphonuclear neutrophils (PMN) and are positively correlated. As an interesting finding, we here detected an early and selective activation of AMPK as key regulatory molecule in parasite-exposed PMN. Furthermore, we document that B. besnoiti-triggered NET structures impair endothelial integrity but fail to significantly alter intracellular development of this parasite in endothelial cells. In addition, metabolic signatures of NETotic PMN indicated a key role of glycolysis and the glucose-pyruvate-lactate-axis. Functional inhibitor studies revealed a species-dependent relevance of monocarboxylate transporters for NETosis on one hand, but emphasized the common pivotal role of purinergic signaling and mitochondrial ATP synthesis for proper functionality of this effector mechanism on the other hand. Moreover, we here showed that chemical treatments of parasitic stages to remove surface carbohydrate residues led to diminished NETosis indicating that glycans may serve as parasite-derived triggers of NETosis. Respective lectin blots indicated a considerable variety of glycans in parasite stages, fluorescence analyses showed that these were present in both, inner compartments and on the surface of tachyzoites and sporozoites.In the current proposal, we want to focus on the following topics to better understand the molecular basis of coccidia-driven NETosis: i) Are parasite surface glycans indeed triggers of coccidian-induced NETosis?, ii) Is ATP a metabolic masterregulator of parasite-driven NET formation?, iii) Does AMPK function as an regulator of early parasite-mediated NETosis?, iv) Which role play parasite-, PMN- or infected host cell-derived extracellular vesicles in parasite-induced NET induction?, and v) Which influence do physiological oxygen conditions have on coccidian-triggered NET formation? With all this effort, we expect to reveal new aspects of the highly complex induction and regulation of parasite-induced NETosis.
球虫寄生虫如贝氏艾美耳球虫(Besnoitia besnoiti)或牛艾美耳球虫(Eimeria bovis)的感染显著损害动物福利并在养牛业中造成高经济损失。总的来说,适当的免疫反应在控制这些寄生虫感染方面发挥着关键作用。在我们最近的工作中,我们确定了几个球虫物种和阶段作为“神经细胞外陷阱”(NET)形成的有效触发因素,这意味着先天免疫细胞的重要效应机制。上述建议的数据表明,NETosis和自噬过程同时发生在寄生虫激活的多形核中性粒细胞(PMN)中,并且呈正相关。作为一个有趣的发现,我们在这里检测到一个早期和选择性激活AMPK作为关键的调节分子在寄生虫暴露的PMN。此外,我们证明了B。besnoiti-triggered NET结构损害内皮完整性,但不能显着改变这种寄生虫在内皮细胞的细胞内发育。此外,NETotic PMN的代谢特征表明糖酵解和葡萄糖-丙酮酸-乳酸轴的关键作用。功能性抑制剂研究一方面揭示了NETosis的单羧酸转运蛋白的物种依赖性相关性,但另一方面强调了嘌呤能信号传导和线粒体ATP合成对于该效应机制的适当功能的共同关键作用。此外,我们在这里表明,化学处理寄生阶段,以消除表面碳水化合物残基导致减少NETosis表明聚糖可能作为寄生虫源性触发NETosis。相应的凝集素印迹表明在寄生虫阶段有相当多的聚糖,荧光分析表明这些聚糖存在于速殖子和子孢子的内部室和表面上。在当前的提议中,我们希望关注以下主题以更好地理解球虫驱动的NETosis的分子基础:i)寄生虫表面聚糖确实是球虫诱导的NETosis的触发剂吗?ii)ATP是寄生虫驱动的NET形成的代谢主调节剂吗?iii)AMPK是否作为早期寄生虫介导的NETosis的调节剂起作用?iv)在寄生虫诱导的NET诱导中,寄生虫、PMN或感染的宿主细胞来源的细胞外囊泡起什么作用?以及v)生理氧条件对球虫触发的NET形成有哪些影响?通过所有这些努力,我们希望揭示寄生虫诱导的NETosis的高度复杂的诱导和调节的新方面。
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)
数据更新时间:{{ journalArticles.updateTime }}
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
数据更新时间:{{ journalArticles.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ monograph.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ sciAawards.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ conferencePapers.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ patent.updateTime }}
Professorin Dr. Anja Taubert其他文献
Professorin Dr. Anja Taubert的其他文献
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
{{ truncateString('Professorin Dr. Anja Taubert', 18)}}的其他基金
Modulation of the host cell cholesterol metabolism by Eimeria bovis
牛美勒藻对宿主细胞胆固醇代谢的调节
- 批准号:
261269677 - 财政年份:2014
- 资助金额:
-- - 项目类别:
Research Grants
Charakterisierung von nicht-adaptiven Immunreaktionen bei Coccidia-Infektionen im Rindersystem
牛系统中球虫感染的非适应性免疫反应的特征
- 批准号:
5418041 - 财政年份:2003
- 资助金额:
-- - 项目类别:
Research Grants
相似海外基金
Persistent micro- and nanoplastics as triggers for interstitial lung disease
持久性微塑料和纳米塑料是间质性肺病的诱因
- 批准号:
MR/Y012682/1 - 财政年份:2024
- 资助金额:
-- - 项目类别:
Research Grant
RAPID: Investigating the Triggers of the 2023 Wrangell, Alaska Landslides
RAPID:调查 2023 年阿拉斯加兰格尔山体滑坡的诱因
- 批准号:
2421234 - 财政年份:2024
- 资助金额:
-- - 项目类别:
Standard Grant
CAREER: Tectonically dead but geomorphologically alive: Investigating the role of hard rocks as triggers of widespread, long-term landscape change in continent interiors
职业:构造上已死,但地貌上却还活着:研究硬岩作为大陆内部广泛、长期景观变化的触发因素的作用
- 批准号:
2340311 - 财政年份:2024
- 资助金额:
-- - 项目类别:
Continuing Grant
A Low-Cost Wearable Connected Health Device for Monitoring Environmental Pollution Triggers of Asthma in Communities with Health Disparities
一种低成本可穿戴互联健康设备,用于监测健康差异社区中哮喘的环境污染诱因
- 批准号:
10601615 - 财政年份:2023
- 资助金额:
-- - 项目类别:
Sensory sensitivity: Mechanisms, triggers and soothers
感官敏感性:机制、触发器和安抚器
- 批准号:
2883583 - 财政年份:2023
- 资助金额:
-- - 项目类别:
Studentship
Cardiac Autonomic Activation In Atrial Fibrillation Triggers And Substrate
心房颤动的心脏自主激活触发因素和基质
- 批准号:
10636441 - 财政年份:2023
- 资助金额:
-- - 项目类别:
An Empirical Study on a Behavioral Model for Invoking the Potential Demand of Micro-Tourism through the Provision of Behavior Change Triggers
通过提供行为改变触发因素激发微旅游潜在需求的行为模型实证研究
- 批准号:
23K11632 - 财政年份:2023
- 资助金额:
-- - 项目类别:
Grant-in-Aid for Scientific Research (C)
Control by Beta 7 integrins of the bacterial triggers of IBD
Beta 7 整合素控制 IBD 细菌触发因素
- 批准号:
10481726 - 财政年份:2023
- 资助金额:
-- - 项目类别:
GLYCANS AS MASTER TRIGGERS OF HEALTH TO INTESTINAL INFLAMMATION TRANSITION
聚糖是健康到肠道炎症转变的主要触发因素
- 批准号:
10064498 - 财政年份:2023
- 资助金额:
-- - 项目类别:
EU-Funded
Applications-oriented elucidation of germination triggers for Emu Bush seed
以应用为导向的鸸鹋种子发芽触发因素的阐明
- 批准号:
LP210301206 - 财政年份:2023
- 资助金额:
-- - 项目类别:
Linkage Projects