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Esther von Stebut-Borschitz (2014-2017)

Functional characterization of cell-specific differences of L. major-containing phagolysosomes in macrophages and dendritic cells (joint project with Stefan Tenzer)

After transmission into the skin by the bite of a sand fly, Leishmania major protozoan parasites are phagocytosed by macrophages, and dendritic cells (DC). The infectious stage promastigote L. major life form is taken up by skin-resident macrophages, in which the parasite transforms into the obligate intracellular life form within the parasite-containing phagolysosome, the parasitophorous vacuole (PV). In contrast, DC preferentially ingest amastigotes. The intracellular events after parasite internalization by these two phagocytes (Macrophages, DC) are not well characterized. However, the fate of the parasite within these cells and their cellular responses differ significantly, e.g. IL-12 release is only observed in DC, but not MF. Recently, we identified intracellular, phagolysosomal TLR9 signalling as critical for DC-derived IL-12 production after infection. Thus, we now intend to further study the constituents and conditions that define the respective L. major-containing PVs in more detail using TEM and an unbiased quantitative proteomic approach to map changes and differences in the proteome of phagocytic vesicles. We aim to chart specific changes in both host and pathogen derived PV components in the two cell types to identify host as well as pathogen-derived factors involved in phagocytosis and PV maintenance as well as pathogen-derived factors characterizing adaptation to the cell-type specific environments encountered.