Project Details
Projekt
Functional characterization of cell-specific differences of L. major-containing phagolysosomes in macrophages and dendritic cells
Subject Area
Immunology
Term
from 2014 to 2017
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 261181825
After transmission into the skin by the bite of a sand fly, Leishmania major protozoan parasites are phagocytosed by macrophages (MF), and dendritic cells (DC). The infectious stage promastigote L. major life form is taken up by skin-resident MF, 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 (MF, DC) are not well characterized. However, the fate of the parasite within these cells and their cellular behaviour 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 exist in the respective L. major-containing PVs in more detail. Using TEM and unbiased systems biology approaches to map changes and differences in the proteome of phagocytic vesicles to chart changes in both host and pathogen transcriptomes after infection in the two cell types, we aim 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 different environments encountered inside the cell types.
DFG Programme
Priority Programmes
