title: Regulation of translation is required for dendritic cell function and survival during activation.
abstract: In response to inflammatory stimulation, dendritic cells (DCs) have a remarkable pattern of differentiation (maturation) that exhibits specific mechanisms to control antigen processing and presentation. Here, we show that in response to lipopolysaccharides, protein synthesis is rapidly enhanced in DCs. This enhancement occurs via a PI3K-dependent signaling pathway and is key for DC activation. In addition, we show that later on, in a manner similar to viral or apoptotic stress, DC activation leads to the phosphorylation and proteolysis of important translation initiation factors, thus inhibiting cap-dependent translation. This inhibition correlates with major changes in the origin of the peptides presented by MHC class I and the ability of mature DCs to prevent cell death. Our observations have important implications in linking translation regulation with DC function and survival during the immune response.
authors.affiliation: Centre d'Immunologie de Marseille-Luminy, Université de la Méditerranée, Case 906, 13288 Marseille, France.
authors.forename: Hugues
authors.initials: H
authors.lastname: Lelouard
authors.forename: Enrico K
authors.initials: EK
authors.lastname: Schmidt
authors.forename: Voahirana
authors.initials: V
authors.lastname: Camosseto
authors.forename: Giovanna
authors.initials: G
authors.lastname: Clavarino
authors.forename: Maurizio
authors.initials: M
authors.lastname: Ceppi
authors.forename: Hsiang-Ting
authors.initials: HT
authors.lastname: Hsu
authors.forename: Philippe
authors.initials: P
authors.lastname: Pierre
mesh_terms: D000818:Animals; D017951:Antigen Presentation / Q000235:genetics*; D002454:Cell Differentiation / Q000235:genetics*; D002470:Cell Survival / Q000235:genetics; D002478:Cells, Cultured; D018388:Codon, Terminator / Q000235:genetics*; D003713:Dendritic Cells / Q000502:physiology*; D039642:Eukaryotic Initiation Factors / Q000235:genetics / Q000378:metabolism*; D015395:Histocompatibility Antigens Class I / Q000378:metabolism; D007111:Immunity, Cellular / Q000235:genetics; D007249:Inflammation / Q000235:genetics / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000235:genetics; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D014176:Protein Biosynthesis / Q000235:genetics*; D015398:Signal Transduction / Q000502:physiology; D015854:Up-Regulation / Q000235:genetics
chemical_list: D018388:Codon, Terminator; D039642:Eukaryotic Initiation Factors; D015395:Histocompatibility Antigens Class I; D008070:Lipopolysaccharides; D019869:Phosphatidylinositol 3-Kinases