Cellular metabolism constrains innate immune responses in early human ontogeny
dc.contributor.author | Kan, Bernard | |
dc.contributor.author | Michalski, Christina | |
dc.contributor.author | Fu, Helen | |
dc.contributor.author | Au, Hilda H.T. | |
dc.contributor.author | Lee, Kelsey | |
dc.contributor.author | Marchant, Elizabeth A. | |
dc.contributor.author | Cheng, Maye F. | |
dc.contributor.author | Anderson-Baucum, Emily | |
dc.contributor.author | Aharoni-Simon, Michal | |
dc.contributor.author | Tilley, Peter | |
dc.contributor.author | Mirmira, Raghavendra G. | |
dc.contributor.author | Ross, Colin J. | |
dc.contributor.author | Luciani, Dan S. | |
dc.contributor.author | Jan, Eric | |
dc.contributor.author | Lavoie, Pascal M. | |
dc.contributor.department | Medicine, School of Medicine | en_US |
dc.date.accessioned | 2019-06-17T14:22:28Z | |
dc.date.available | 2019-06-17T14:22:28Z | |
dc.date.issued | 2018-11-16 | |
dc.description.abstract | Pathogen immune responses are profoundly attenuated in fetuses and premature infants, yet the mechanisms underlying this developmental immaturity remain unclear. Here we show transcriptomic, metabolic and polysome profiling and find that monocytes isolated from infants born early in gestation display perturbations in PPAR-γ-regulated metabolic pathways, limited glycolytic capacity and reduced ribosomal activity. These metabolic changes are linked to a lack of translation of most cytokines and of MALT1 signalosome genes essential to respond to the neonatal pathogen Candida. In contrast, they have little impact on house-keeping phagocytosis functions. Transcriptome analyses further indicate a role for mTOR and its putative negative regulator DNA Damage Inducible Transcript 4-Like in regulating these metabolic constraints. Our results provide a molecular basis for the broad susceptibility to multiple pathogens in these infants, and suggest that the fetal immune system is metabolically programmed to avoid energetically costly, dispensable and potentially harmful immune responses during ontogeny. | en_US |
dc.eprint.version | Final published version | en_US |
dc.identifier.citation | Kan, B., Michalski, C., Fu, H., Au, H., Lee, K., Marchant, E. A., … Lavoie, P. M. (2018). Cellular metabolism constrains innate immune responses in early human ontogeny. Nature communications, 9(1), 4822. doi:10.1038/s41467-018-07215-9 | en_US |
dc.identifier.uri | https://hdl.handle.net/1805/19621 | |
dc.language.iso | en_US | en_US |
dc.publisher | Nature Research | en_US |
dc.relation.isversionof | 10.1038/s41467-018-07215-9 | en_US |
dc.relation.journal | Nature Communications | en_US |
dc.rights | Attribution 3.0 United States | * |
dc.rights.uri | http://creativecommons.org/licenses/by/3.0/us/ | * |
dc.source | PMC | en_US |
dc.subject | B-Cell CLL-Lymphoma 10 Protein | en_US |
dc.subject | CARD Signaling Adaptor Proteins | en_US |
dc.subject | Candida albicans | en_US |
dc.subject | Candida parapsilosis | en_US |
dc.subject | Gene Expression Regulation, Developmental | en_US |
dc.subject | Immunity, Innate | en_US |
dc.subject | Infant, Newborn | en_US |
dc.subject | Infant, Premature | en_US |
dc.subject | Interleukins | en_US |
dc.subject | Lectins, C-Type | en_US |
dc.subject | Microarray Analysis | en_US |
dc.subject | Monocytes | en_US |
dc.subject | Mucosa-Associated Lymphoid Tissue Lymphoma Translocation 1 Protein | en_US |
dc.subject | PPAR gamma | en_US |
dc.subject | Primary Cell Culture | en_US |
dc.subject | Protein Biosynthesis | en_US |
dc.subject | TOR Serine-Threonine Kinases | en_US |
dc.subject | Transcription Factors | en_US |
dc.subject | Transcriptome | en_US |
dc.subject | Tumor Necrosis Factor-alpha | en_US |
dc.title | Cellular metabolism constrains innate immune responses in early human ontogeny | en_US |
dc.type | Article | en_US |
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