"Dendritic cells (DC) are professional antigen-presenting cells that represent an essential link between innate and adaptive immunity. While DC maturation is triggered by direct toll-like receptor engagement, it can also be initiated when DC interact with other cell types acting at the innate phase of the immune response like gamma delta T cells and natural killer (NK) cells. Gamma T cells can induce DC maturation and, when activated, induce the production of IL-12, an effect that involves gamma delta T cell-derived IFN-gamma. Interestingly, it has been recently shown that neonatal gamma delta T cells, in contrast to neonatal gamma delta T cells, are not deficient in IFN-gamma production. Also a cross-talk between DC and NK cells has been demonstrated. The primary objective is to identify strategies that might overcome the inability of neonatal DC to produce bioactive IL-12. This will contribute to the development of new adjuvants able to induce efficient Th1-type responses in human neonates. As it has been shown that IFN-gamma restores IL-12 production in neonatal DC, the focus will be to find cellular sources of IFN-gamma in human newborn. The primary candidates we will investigate are gamma delta T cells and NK cells. In a second line of research, we will t ry to identify new molecules involved in the maturation of the neonatal immune system via an unbiased approach, namely DNA microarrays. The expertise of the host institute (dendritic cells, neonatal immunology) clearly complements the background of David Vermijlen (human gamma delta T cells, NK cells, microarray experience) that will result in a synergistic effect and contribute to the scientific excellence of the European Union. In addition, David Vermijlen will return to Belgium, his country of origin, to become professionally integrated. Therefore, the proposed project fully meets the objectives of the Marie-Curie European reintegration grant."
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