The Effect Of Malaria Parasites On Dendritic Cell Metabolism (TEMPODM)

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Children in malaria endemic regions have weakened immune responses against immune challenges, such as infection or childhood vaccines. This poses a particularly significant problem for malaria vaccines, which have been much less successful in malaria exposed, compared with non-exposed (western) populations. Research by our team, and others, has led to the hypothesis that malaria blocks the physical interaction of two key immune cells, T cells and Dendritic Cells (DC). The interaction of T cells with DC is essential to form a protective immune response to infections or vaccines. To understand why this happens, we found that when malaria parasites are eaten by DC they damage the key generators of cellular energy, called mitochondria. While this should cause DC to die, we have shown that DC adapt by using other energy generating approaches to stay alive. We believe that this loss of power, or the adaptation process resulting from this, produces the failure in DC function during malaria infection. These processes are also of interest to cancer researchers, as an important way for tumour cells to stay alive, as a result, there are many drugs available to interfere with these processes. We can therefore use these drugs as tools to understand which aspects of adaptation are important in loss of DC function, and whether these allow T/DC interactions to proceed. Finally, we hypothesise that identifying drugs that can re-establish T cell/DC interactions in the face of malaria can be used enhance protective vaccination in malaria endemic regions.