Regulation of translation is required for dendritic cell function and survival during activation.
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.
Lelouard
Hugues
H
Centre d'Immunologie de Marseille-Luminy, Université de la Méditerranée, Case 906, 13288 Marseille, France.
Schmidt
Enrico K
EK
Camosseto
Voahirana
V
Clavarino
Giovanna
G
Ceppi
Maurizio
M
Hsu
Hsiang-Ting
HT
Pierre
Philippe
P
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
D018388:Codon, Terminator; D039642:Eukaryotic Initiation Factors; D015395:Histocompatibility Antigens Class I; D008070:Lipopolysaccharides; D019869:Phosphatidylinositol 3-Kinases