Characterization of a novel nucleotide based second messenger system regulating innate immune responses

调节先天免疫反应的新型核苷酸第二信使系统的表征

• 批准号: 423400107
• 负责人: Professor Dr. Andreas Pichlmair
• 金额: --
• 依托单位: Institut für Virologie (aufgelöst)
• 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 2022-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/423400107?language=en
• 关键词: Characterization; novel; nucleotide; based; second

The innate immune system is essential for the successful clearance of pathogens such as viruses and bacteria. It consists of a network including sensors and signaling cascades and leads to the synthesis of antiviral proteins and regulation of the immune system. Various ways evolved to transmit the signal from sensor proteins to downstream effector functions. These include direct protein-protein interactions and cytokines, which are protein based messenger molecules. An alternative way to transmit signals involves nucleotide-based messengers called "second messengers". Here I apply for funding to study a yet unappreciated novel signaling cascade that involves the activity of di-adenosine tetraphosphate (AP4A). AP4A stimulated human monocytes and murine bone marrow generate cytokines through a yet unstudied signaling cascade. Here I propose to study the generation of AP4A, the involved singalling cascade and the effects that AP4A has on an organismal level. We hypothesize that this mechanism is used to identify infected cells in tissue and to regulate the antiviral immune response.

先天免疫系统对于成功清除病毒和细菌等病原体至关重要。它由一个包括传感器和信号级联的网络组成，并导致抗病毒蛋白质的合成和免疫系统的调节。进化出多种途径将信号从传感蛋白传递到下游效应功能。这些包括直接的蛋白质-蛋白质相互作用和细胞因子，它们是基于蛋白质的信使分子。另一种传输信号的方式涉及基于核苷酸的信使，称为“第二信使”。在这里，我申请资金来研究一个尚未被认识的新型信号级联，涉及四磷酸二腺苷（AP4A）的活性。AP4A刺激人类单核细胞和小鼠骨髓通过尚未研究的信号级联产生细胞因子。在这里，我建议研究AP4A的产生，所涉及的信号级联以及AP4A在机体水平上的影响。我们假设这种机制被用来识别组织中的感染细胞并调节抗病毒免疫反应。