Cyclic nucleotide signalling in innate immunity

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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.