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

先天免疫系统对于病毒和细菌等病原体的成功清除是必不可少的。它由一个包括传感器和信号级联的网络组成，并导致抗病毒蛋白的合成和免疫系统的调节。进化出了多种方式来将信号从传感器蛋白传递到下游的效应器功能。这些包括蛋白质与蛋白质的直接相互作用和细胞因子，它们是基于蛋白质的信使分子。另一种传递信号的方式涉及被称为“第二信使”的基于核苷酸的信使。在这里，我申请资金来研究一个尚未被赏识的新的信号级联，它涉及到二腺苷四磷酸(AP4A)的活性。AP4A刺激的人单核细胞和小鼠骨髓通过尚未研究过的信号级联反应产生细胞因子。在这里，我建议研究AP4A的产生，涉及的信号级联，以及AP4A在生物体水平上的影响。我们推测，这种机制被用来识别组织中的受感染细胞，并调节抗病毒免疫反应。

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.