Cyclic nucleotide signalling in innate immunity

动物的免疫功能对抗感染的可能影响。在昆虫中，存在一种古老的免疫形式，它形成了人类和动物免疫系统的模板。在微小的果蝇中进行的研究，使用肾脏的昆虫类似物（Malpighian tubule），已经表明这种组织本身可以感知免疫攻击，并可以赋予整个动物免疫状态。这表明，外周组织，如肾脏，可能比以前认为的更重要，在整个身体的免疫监视。肾小管如何进行免疫防御？我们有证据表明，一个简单的分子，环GMP，调节基因表达的一组关键的抗微生物防御肽在肾小管。这可能会影响整个动物的免疫状态。申请中描述的研究将使我们能够研究cGMP如何设置免疫状态的水平。由于cGMP在人类中也存在，并且以与果蝇相似的方式起作用，因此我们有可能通过研究这些分子如何在果蝇中起作用来发现新的免疫调节剂。这可能对昆虫害虫控制策略（许多昆虫是人类疾病的主要媒介）和潜在的新治疗药物的评估都有重要影响，这些药物用于控制各种疾病条件下这些小分子的水平。

Immune function in animals counters the possible effects of infection. In insects, an ancient form of immunity exists, which forms the template for human and animal immune systems. Studies conducted in the tiny fruit fly, Drosophila, using the insect analogue of the kidney (Malpighian tubule), have shown that this tissue itself can sense an immune attack, and can confer immune status on the whole animal. This suggests that peripheral tissue such as kidney may be more important than previously thought in immune surveillance for the whole body. How does the tubule mount an immune defense? We have evidence that a simple molecule, cyclic GMP, regulates gene expression of a key set of anti-microbial defence peptides in the tubule. This can affect the immune status of the entire animal. The studies described in the application will allow us to work out how cGMP can set the level of the immune state. As cGMP also exists and works in a similar way in humans as in the fly, it is possible that we may uncover new modulators of immunity by working out how such molecules work in Drosophila. This may have important consequences for both insect pest control strategies (many insects are major vectors of human disease) and also in the assessment of potential new therapeutic drugs, that act to control levels of these small molecules in various disease conditions.