Influence of Fcγ receptor distribution on mannose receptor mediated phagocytosis

In this study the recognition maps obtained by the simultaneous topography and recognition (TREC) imaging revealed that Fcγ receptors are distributed in micro-domains of sizes 4nm to 200nm. The fluorescent and electron-microscopy provided further evidence that these clusters are located within close proximity of mannose receptors. This pattern of distribution of FcγRs and MRs led to inhibition of the MR mediated mediated phagocytosis. The data presented in this thesis provide evidences of cross-talk between FcγR mediated and MR mediated phagocytosis.Die vorliegende Arbeit zeigt mit Hilfe des TREC-Imagings (topography and recognition), dass Fcγ-Rezeptoren (FcγR) in Mikrodomänen verschiedener Größe (2-200nm) verteilt sind. Fluoreszenz- und elektronenmikroskopische Untersuchungen enthüllten, dass diese Domänen in enger Nachbarschaft von Mannoserezeptoren (MR) liegen. Dieses Verteilungsmuster von FcγRs und MRs führt zur Inhibierung der MR-vermittelten Phagozytose. Zusammenfassend belegen die gewonnen Daten, dass es ein Zusammenspiel zwischen FcγR-vermittelter und MR-vermittelter Phagozytose gibt

Initial receptor-ligand interactions modulate gene expression and phagosomal properties during both early and late stages of phagocytosis

International audienceThe receptors engaged during recognition and phagocytic uptake of microorganisms and particles influence signaling events and diverse subcellular responses that occur during phagosome formation and maturation. However, pathogens generally have multiple ligands on their surface, making it difficult to dissect the roles of individual receptors during phagocytosis. Moreover,it remains elusive to which extent receptor-ligand interactions and early binding events define the subsequent intracellular fate of phagosomes. Here,we used latex beads coupled to single ligands, focusing on immunoglobulin G, man- nan, bacterial lipopolysaccharides and avidin, and monitored: (1) phagocytic uptake rates, (2) fusion of phagosomes with lysosomal compartments,(3) the gene expression profile during phagocytosis, (4) the protein composition of mature phagosomes, and (5) time-dependent dynamics of protein association with phagosomes in J774.A1 mouse macrophages. The differently coated latex beads were internalized at different rates and exhibited different kinetics of phagolysosomal fusion events dependent on their specific ligand. Furthermore, less than 60% of identified phagosomal proteins and only 10 -1 5% of changes in gene expression were common to all investigated ligands. These findings demonstrate that each single ligand induced a distinct pattern of genes and a different protein composition of phagosomes.Taken together, our data argue that phagocytic receptor-specific programs of signaling events direct phagosomes to different physiological states and support the existence of a specific receptor-ligand 'signature' during the whole process of phagocytosis