title: Initial receptor-ligand interactions modulate gene expression and phagosomal properties during both early and late stages of phagocytosis.
abstract: The 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, mannan, 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 10-15% 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.
authors.affiliation: Institute of Biological Sciences, University of Rostock, Rostock, Germany. eik.hoffmann@curie.fr
authors.forename: Eik
authors.initials: E
authors.lastname: Hoffmann
authors.forename: Sabrina
authors.initials: S
authors.lastname: Marion
authors.forename: Bibhuti Bhusan
authors.initials: BB
authors.lastname: Mishra
authors.forename: Mathias
authors.initials: M
authors.lastname: John
authors.forename: Ramona
authors.initials: R
authors.lastname: Kratzke
authors.forename: Syed Furquan
authors.initials: SF
authors.lastname: Ahmad
authors.forename: Daniela
authors.initials: D
authors.lastname: Holzer
authors.forename: Paras Kumar
authors.initials: PK
authors.lastname: Anand
authors.forename: Dieter G
authors.initials: DG
authors.lastname: Weiss
authors.forename: Gareth
authors.initials: G
authors.lastname: Griffiths
authors.forename: Sergei A
authors.initials: SA
authors.lastname: Kuznetsov
mesh_terms: D000818:Animals; D005455:Fluorescent Antibody Technique; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D007425:Intracellular Membranes / Q000378:metabolism; D008024:Ligands; D013058:Mass Spectrometry; D051379:Mice; D046228:Microarray Analysis; D018613:Microscopy, Confocal; D010587:Phagocytosis / Q000502:physiology*; D010588:Phagosomes / Q000378:metabolism / Q000502:physiology* / Q000648:ultrastructure; D011485:Protein Binding; D015398:Signal Transduction
chemical_list: D008024:Ligands