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Sensing and Signalling in the Innate Immune Response, using Drosophila as a Model

Final Report Summary - IMMUDROSO (Sensing and Signalling in the Innate Immune Response, using Drosophila as a Model.)

The adaptive immune system, with its antibodies and lymphocytes, is the hallmark of humans and other vertebrates. This adaptive system is extremely powerful, but requires that many cells be dedicated to making antibodies, which is only possible for a large organism. Specific antibodies are produced, which are targeted to individual microbes, but it takes several weeks to develop new antibodies when a novel pathogen infects the body. During this lag period, it is the innate immune response that keeps us alive and fights off the pathogen attack. The innate immune system is activated in the early stages of an infection and is essential to trigger an efficient adaptive response. Like all other invertebrates, the fruit fly, Drosophila melanogaster defends itself against microbes with a purely innate immune response. Our work on the innate immune system in flies, and particularly the discovery of the role of the Toll receptor, was the breakthrough that led to the explosion of our knowledge on the importance of the innate immune system in humans, recognised by the award of the Nobel Prize for Medicine in 2011.
The aim of the “IMMUDROSO” project was to further exploit the fruit fly model system to obtain a better understanding of how the innate immune system is controlled. The conserved mammalian NF-κB transcription factor is at the centre of our immune response and every aspect of inflammation. We have now characterized new layers of regulatory control, which show how NF-κB selectively activates different subsets of downstream genes. In particular, we have identified a novel control mechanism of inflammation, in this study, that is conserved between flies and man. This regulatory control, centred around the Akirin gene, presents ideal drug targets for therapeutic intervention against inflammatory diseases. This exciting new area of research should lead to a better understanding of the control of immune reactions, one of the most important goals for medical research in the next decade.