Dendritic cells act as the immune system’s messengers, ferrying fragments of microbes or vaccines from the site of infection to the T lymphocytes that orchestrate a full immune response. This project investigates the earliest moments of that process—what happens when a dendritic cell first senses a bacterial or viral product. The researchers have discovered that these cells “wake up” from a resting state, boosting their ability to capture and process foreign material. They are also studying podosomes, tiny structures that may help dendritic cells migrate through tissues to reach T cells. The gap in knowledge is that vaccine designers currently lack a detailed understanding of these early biochemical signals and movements. If this fundamental science succeeds, it will reveal the precise signalling events that trigger efficient uptake and migration. That knowledge could eventually allow vaccines to be engineered for better delivery—taken up more readily by dendritic cells and carried more swiftly to the sites where immunity is activated. This is curiosity-driven research, but similar work on immune cell biology has previously underpinned advances in vaccine design, from adjuvants to mRNA delivery systems.
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Several important cells in our immune system collaborate when we are infected with a microbe or when we are vaccinated against one to activate an ?immune response?. In most cases the first cells to encounter the invader or vaccine are so called dendritic cells (DC). These cells act as messengers which ferry a processed form of the microbe or vaccine from the site of vaccination to the specialised sites in the body where other immune cells, particularly lymphocytes, are waiting to be activated. The coming together of dendritic cells and so called T lymphocytes is a key event that ultimately leads to elimination of the invader and/or to the creation of a ?memory? to allow a faster response to the same insult in the future. Many immunologists believe that better understanding of the biology of dendritic cells will help in the design of new and better performing vaccines. We are working on the early events that occur when dendritic cells encounter foreign material whether it be a vaccine or the actual pathogen. We have found that DC ?wake up? from a resting state when they sense bacterial or viral products and boost their ability to capture and process foreign material so that they can better display it to T cells. We are also studying intriguing structures called podosomes that are thought to be relevant to the journey that dendritic cells make out of the tissues towards their encounter with T cells. We have been studying the detailed biochemical signalling events that are triggered in dendritic cells by microbial material and how podosomes might be involved in aiding migration of dendritic cells. We think that more detailed knowledge will allow vaccines to be designed that are taken up more efficiently by dendritic cells and which boost their migration from the tissues to the sites where collaborations with lymphocytes take place.
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