Microbial stimulation of different Toll-like receptor signalling pathways induces diverse metabolic programmes in human monocytes View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

2017-03

AUTHORS

Ekta Lachmandas, Lily Boutens, Jacqueline M. Ratter, Anneke Hijmans, Guido J. Hooiveld, Leo A. B. Joosten, Richard J. Rodenburg, Jack A. M. Fransen, Riekelt H. Houtkooper, Reinout van Crevel, Mihai G. Netea, Rinke Stienstra

ABSTRACT

Microbial stimuli such as lipopolysaccharide (LPS) induce robust metabolic rewiring in immune cells known as the Warburg effect. It is unknown whether this increase in glycolysis and decrease in oxidative phosphorylation (OXPHOS) is a general characteristic of monocytes that have encountered a pathogen. Using CD14+ monocytes from healthy donors, we demonstrated that most microbial stimuli increased glycolysis, but that only stimulation of Toll-like receptor (TLR) 4 with LPS led to a decrease in OXPHOS. Instead, activation of other TLRs, such as TLR2 activation by Pam3CysSK4 (P3C), increased oxygen consumption and mitochondrial enzyme activity. Transcriptome and metabolome analysis of monocytes stimulated with P3C versus LPS confirmed the divergent metabolic responses between both stimuli, and revealed significant differences in the tricarboxylic acid cycle, OXPHOS and lipid metabolism pathways following stimulation of monocytes with P3C versus LPS. At a functional level, pharmacological inhibition of complex I of the mitochondrial electron transport chain diminished cytokine production and phagocytosis in P3C- but not LPS-stimulated monocytes. Thus, unlike LPS, complex microbial stimuli and the TLR2 ligand P3C induce a specific pattern of metabolic rewiring that involves upregulation of both glycolysis and OXPHOS, which enables activation of host defence mechanisms such as cytokine production and phagocytosis. More... »

PAGES

nmicrobiol2016246

References to SciGraph publications

  • 1979-06. The influence of some metabolic inhibitors on phagocytic activity of mouse macrophages in vitro in RESEARCH IN EXPERIMENTAL MEDICINE
  • 2014-04. TLR-driven early glycolytic reprogramming via the kinases TBK1-IKKɛ supports the anabolic demands of dendritic cell activation in NATURE IMMUNOLOGY
  • 2013-04. Succinate is an inflammatory signal that induces IL-1β through HIF-1α in NATURE
  • 2006-12. Intensity-based hierarchical Bayes method improves testing for differentially expressed genes in microarray experiments in BMC BIOINFORMATICS
  • 2014-09. Cell-intrinsic lysosomal lipolysis is essential for alternative activation of macrophages in NATURE IMMUNOLOGY
  • 2016-09. A guide to immunometabolism for immunologists in NATURE REVIEWS IMMUNOLOGY
  • 2009-07. Enhancing CD8 T-cell memory by modulating fatty acid metabolism in NATURE
  • 1979-01. Phagocytosis and cellular metabolism in INTERNATIONAL JOURNAL OF CLINICAL AND LABORATORY RESEARCH
  • 2013-06. Methods for defining distinct bioenergetic profiles in platelets, lymphocytes, monocytes, and neutrophils, and the oxidative burst from human blood in LABORATORY INVESTIGATION
  • 2007-06-28. Macrophage-specific PPARγ controls alternative activation and improves insulin resistance in NATURE
  • 2011-04. Biochemical diagnosis of mitochondrial disorders in JOURNAL OF INHERITED METABOLIC DISEASE
  • 2015-07. Metabolic reprogramming in macrophages and dendritic cells in innate immunity in CELL RESEARCH
  • 2016-04. Broad defects in the energy metabolism of leukocytes underlie immunoparalysis in sepsis in NATURE IMMUNOLOGY
  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/nmicrobiol.2016.246

    DOI

    http://dx.doi.org/10.1038/nmicrobiol.2016.246

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1006234853

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/27991883


    Indexing Status Check whether this publication has been indexed by Scopus and Web Of Science using the SN Indexing Status Tool
    Incoming Citations Browse incoming citations for this publication using opencitations.net

    JSON-LD is the canonical representation for SciGraph data.

    TIP: You can open this SciGraph record using an external JSON-LD service: JSON-LD Playground Google SDTT

    [
      {
        "@context": "https://springernature.github.io/scigraph/jsonld/sgcontext.json", 
        "about": [
          {
            "id": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/1107", 
            "inDefinedTermSet": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/", 
            "name": "Immunology", 
            "type": "DefinedTerm"
          }, 
          {
            "id": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/11", 
            "inDefinedTermSet": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/", 
            "name": "Medical and Health Sciences", 
            "type": "DefinedTerm"
          }
        ], 
        "author": [
          {
            "affiliation": {
              "alternateName": "Radboud University Nijmegen Medical Centre", 
              "id": "https://www.grid.ac/institutes/grid.10417.33", 
              "name": [
                "Department of Internal Medicine and Radboud Center for Infectious Diseases, Radboud University Medical Center, 6525 GA, Nijmegen, The Netherlands"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Lachmandas", 
            "givenName": "Ekta", 
            "id": "sg:person.01074074465.58", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01074074465.58"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Wageningen University & Research", 
              "id": "https://www.grid.ac/institutes/grid.4818.5", 
              "name": [
                "Department of Internal Medicine and Radboud Center for Infectious Diseases, Radboud University Medical Center, 6525 GA, Nijmegen, The Netherlands", 
                "Nutrition, Metabolism and Genomics Group, Division of Human Nutrition, Wageningen University, 6708 WE, Wageningen, The Netherlands"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Boutens", 
            "givenName": "Lily", 
            "id": "sg:person.0611166036.68", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0611166036.68"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Wageningen University & Research", 
              "id": "https://www.grid.ac/institutes/grid.4818.5", 
              "name": [
                "Department of Internal Medicine and Radboud Center for Infectious Diseases, Radboud University Medical Center, 6525 GA, Nijmegen, The Netherlands", 
                "Nutrition, Metabolism and Genomics Group, Division of Human Nutrition, Wageningen University, 6708 WE, Wageningen, The Netherlands"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Ratter", 
            "givenName": "Jacqueline M.", 
            "id": "sg:person.015557745415.11", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.015557745415.11"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Radboud University Nijmegen Medical Centre", 
              "id": "https://www.grid.ac/institutes/grid.10417.33", 
              "name": [
                "Department of Internal Medicine and Radboud Center for Infectious Diseases, Radboud University Medical Center, 6525 GA, Nijmegen, The Netherlands"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Hijmans", 
            "givenName": "Anneke", 
            "id": "sg:person.01252630204.02", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01252630204.02"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Wageningen University & Research", 
              "id": "https://www.grid.ac/institutes/grid.4818.5", 
              "name": [
                "Nutrition, Metabolism and Genomics Group, Division of Human Nutrition, Wageningen University, 6708 WE, Wageningen, The Netherlands"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Hooiveld", 
            "givenName": "Guido J.", 
            "id": "sg:person.01054123502.11", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01054123502.11"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Radboud University Nijmegen Medical Centre", 
              "id": "https://www.grid.ac/institutes/grid.10417.33", 
              "name": [
                "Department of Internal Medicine and Radboud Center for Infectious Diseases, Radboud University Medical Center, 6525 GA, Nijmegen, The Netherlands"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Joosten", 
            "givenName": "Leo A. B.", 
            "id": "sg:person.014645240657.77", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.014645240657.77"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Radboud University Nijmegen Medical Centre", 
              "id": "https://www.grid.ac/institutes/grid.10417.33", 
              "name": [
                "Department of Pediatrics, Radboud Center for Mitochondrial Medicine, 774 Translational Metabolic Laboratory, Radboud University Medical Center, 6525 GA, Nijmegen, The Netherlands"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Rodenburg", 
            "givenName": "Richard J.", 
            "id": "sg:person.013350644377.65", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.013350644377.65"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Radboud University Nijmegen Medical Centre", 
              "id": "https://www.grid.ac/institutes/grid.10417.33", 
              "name": [
                "Department of Cell Biology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, 1105 AZ, Nijmegen, The Netherlands"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Fransen", 
            "givenName": "Jack A. M.", 
            "id": "sg:person.01143155310.36", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01143155310.36"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Academic Medical Center", 
              "id": "https://www.grid.ac/institutes/grid.5650.6", 
              "name": [
                "Laboratory Genetic Metabolic Diseases, Academic Medical Center, 1105 AZ, Amsterdam, The Netherlands"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Houtkooper", 
            "givenName": "Riekelt H.", 
            "id": "sg:person.0607551400.36", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0607551400.36"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Radboud University Nijmegen Medical Centre", 
              "id": "https://www.grid.ac/institutes/grid.10417.33", 
              "name": [
                "Department of Internal Medicine and Radboud Center for Infectious Diseases, Radboud University Medical Center, 6525 GA, Nijmegen, The Netherlands"
              ], 
              "type": "Organization"
            }, 
            "familyName": "van Crevel", 
            "givenName": "Reinout", 
            "id": "sg:person.01021435034.00", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01021435034.00"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Radboud University Nijmegen Medical Centre", 
              "id": "https://www.grid.ac/institutes/grid.10417.33", 
              "name": [
                "Department of Internal Medicine and Radboud Center for Infectious Diseases, Radboud University Medical Center, 6525 GA, Nijmegen, The Netherlands"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Netea", 
            "givenName": "Mihai G.", 
            "id": "sg:person.01263677437.18", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01263677437.18"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Wageningen University & Research", 
              "id": "https://www.grid.ac/institutes/grid.4818.5", 
              "name": [
                "Department of Internal Medicine and Radboud Center for Infectious Diseases, Radboud University Medical Center, 6525 GA, Nijmegen, The Netherlands", 
                "Nutrition, Metabolism and Genomics Group, Division of Human Nutrition, Wageningen University, 6708 WE, Wageningen, The Netherlands"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Stienstra", 
            "givenName": "Rinke", 
            "id": "sg:person.01010523164.38", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01010523164.38"
            ], 
            "type": "Person"
          }
        ], 
        "citation": [
          {
            "id": "https://doi.org/10.1074/jbc.m113.454538", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1000333062"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/labinvest.2013.53", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1001640730", 
              "https://doi.org/10.1038/labinvest.2013.53"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/nri.2016.70", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1003163126", 
              "https://doi.org/10.1038/nri.2016.70"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.4049/jimmunol.0901698", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1005113830"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1074/jbc.m110.107854", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1006352899"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1007/bf01851332", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1006918424", 
              "https://doi.org/10.1007/bf01851332"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/nature08097", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1007048279", 
              "https://doi.org/10.1038/nature08097"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/nature08097", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1007048279", 
              "https://doi.org/10.1038/nature08097"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1093/bioinformatics/19.2.185", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1011853799"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1373/clinchem.2006.078873", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1014549350"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1093/nar/gng015", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1018638362"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1074/jbc.m115.662114", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1020882885"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1016/j.cmet.2014.12.005", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1021097318"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1016/j.cmet.2014.12.005", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1021097318"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1016/s1074-7613(00)80119-3", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1022947328"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/ni.2833", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1027192784", 
              "https://doi.org/10.1038/ni.2833"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1002/eji.200636398", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1030199382"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1002/eji.200636398", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1030199382"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1182/blood-2009-10-249540", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1030672391"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1085/jgp.8.6.519", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1031385086"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/cr.2015.68", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1033519755", 
              "https://doi.org/10.1038/cr.2015.68"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1371/journal.pone.0097702", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1034064364"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1186/1471-2105-7-538", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1034318296", 
              "https://doi.org/10.1186/1471-2105-7-538"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1016/j.tcb.2013.11.008", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1036237735"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/ni.2956", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1038049925", 
              "https://doi.org/10.1038/ni.2956"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1093/nar/gni179", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1040526112"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.3389/fimmu.2014.00420", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1042494326"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1007/s10545-010-9081-y", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1042592863", 
              "https://doi.org/10.1007/s10545-010-9081-y"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/ni.3398", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1043334409", 
              "https://doi.org/10.1038/ni.3398"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1074/jbc.m114.603589", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1045299996"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1182/blood-2006-02-002477", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1046435094"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1016/s0022-510x(97)05379-3", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1046435103"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1016/j.immuni.2015.02.005", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1046964949"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1073/pnas.0308496101", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1047153110"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1093/nar/gkv380", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1047923881"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1016/j.cell.2016.05.035", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1048638138"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1152/ajpregu.00584.2012", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1049140409"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/nature05894", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1050655831", 
              "https://doi.org/10.1038/nature05894"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1016/j.cmet.2016.06.004", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1050820088"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/nature11986", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1051643661", 
              "https://doi.org/10.1038/nature11986"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.4049/jimmunol.1003613", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1053705985"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1021/ja2070889", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1055850799"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1021/ja2070889", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1055850799"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://app.dimensions.ai/details/publication/pub.1076688690", 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.4049/jimmunol.1403045", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1079122929"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1007/bf02905027", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1080698775", 
              "https://doi.org/10.1007/bf02905027"
            ], 
            "type": "CreativeWork"
          }
        ], 
        "datePublished": "2017-03", 
        "datePublishedReg": "2017-03-01", 
        "description": "Microbial stimuli such as lipopolysaccharide (LPS) induce robust metabolic rewiring in immune cells known as the Warburg effect. It is unknown whether this increase in glycolysis and decrease in oxidative phosphorylation (OXPHOS) is a general characteristic of monocytes that have encountered a pathogen. Using CD14+ monocytes from healthy donors, we demonstrated that most microbial stimuli increased glycolysis, but that only stimulation of Toll-like receptor (TLR) 4 with LPS led to a decrease in OXPHOS. Instead, activation of other TLRs, such as TLR2 activation by Pam3CysSK4 (P3C), increased oxygen consumption and mitochondrial enzyme activity. Transcriptome and metabolome analysis of monocytes stimulated with P3C versus LPS confirmed the divergent metabolic responses between both stimuli, and revealed significant differences in the tricarboxylic acid cycle, OXPHOS and lipid metabolism pathways following stimulation of monocytes with P3C versus LPS. At a functional level, pharmacological inhibition of complex I of the mitochondrial electron transport chain diminished cytokine production and phagocytosis in P3C- but not LPS-stimulated monocytes. Thus, unlike LPS, complex microbial stimuli and the TLR2 ligand P3C induce a specific pattern of metabolic rewiring that involves upregulation of both glycolysis and OXPHOS, which enables activation of host defence mechanisms such as cytokine production and phagocytosis.", 
        "genre": "research_article", 
        "id": "sg:pub.10.1038/nmicrobiol.2016.246", 
        "inLanguage": [
          "en"
        ], 
        "isAccessibleForFree": false, 
        "isFundedItemOf": [
          {
            "id": "sg:grant.3797303", 
            "type": "MonetaryGrant"
          }
        ], 
        "isPartOf": [
          {
            "id": "sg:journal.1052984", 
            "issn": [
              "2058-5276"
            ], 
            "name": "Nature Microbiology", 
            "type": "Periodical"
          }, 
          {
            "issueNumber": "3", 
            "type": "PublicationIssue"
          }, 
          {
            "type": "PublicationVolume", 
            "volumeNumber": "2"
          }
        ], 
        "name": "Microbial stimulation of different Toll-like receptor signalling pathways induces diverse metabolic programmes in human monocytes", 
        "pagination": "nmicrobiol2016246", 
        "productId": [
          {
            "name": "readcube_id", 
            "type": "PropertyValue", 
            "value": [
              "1db31b62dec457c71b4753c11f88cbe297be9df45d5e2a90936c265d20945a42"
            ]
          }, 
          {
            "name": "pubmed_id", 
            "type": "PropertyValue", 
            "value": [
              "27991883"
            ]
          }, 
          {
            "name": "nlm_unique_id", 
            "type": "PropertyValue", 
            "value": [
              "101674869"
            ]
          }, 
          {
            "name": "doi", 
            "type": "PropertyValue", 
            "value": [
              "10.1038/nmicrobiol.2016.246"
            ]
          }, 
          {
            "name": "dimensions_id", 
            "type": "PropertyValue", 
            "value": [
              "pub.1006234853"
            ]
          }
        ], 
        "sameAs": [
          "https://doi.org/10.1038/nmicrobiol.2016.246", 
          "https://app.dimensions.ai/details/publication/pub.1006234853"
        ], 
        "sdDataset": "articles", 
        "sdDatePublished": "2019-04-10T23:11", 
        "sdLicense": "https://scigraph.springernature.com/explorer/license/", 
        "sdPublisher": {
          "name": "Springer Nature - SN SciGraph project", 
          "type": "Organization"
        }, 
        "sdSource": "s3://com-uberresearch-data-dimensions-target-20181106-alternative/cleanup/v134/2549eaecd7973599484d7c17b260dba0a4ecb94b/merge/v9/a6c9fde33151104705d4d7ff012ea9563521a3ce/jats-lookup/v90/0000000001_0000000264/records_8693_00000421.jsonl", 
        "type": "ScholarlyArticle", 
        "url": "http://www.nature.com/articles/nmicrobiol2016246"
      }
    ]
     

    Download the RDF metadata as:  json-ld nt turtle xml License info

    HOW TO GET THIS DATA PROGRAMMATICALLY:

    JSON-LD is a popular format for linked data which is fully compatible with JSON.

    curl -H 'Accept: application/ld+json' 'https://scigraph.springernature.com/pub.10.1038/nmicrobiol.2016.246'

    N-Triples is a line-based linked data format ideal for batch operations.

    curl -H 'Accept: application/n-triples' 'https://scigraph.springernature.com/pub.10.1038/nmicrobiol.2016.246'

    Turtle is a human-readable linked data format.

    curl -H 'Accept: text/turtle' 'https://scigraph.springernature.com/pub.10.1038/nmicrobiol.2016.246'

    RDF/XML is a standard XML format for linked data.

    curl -H 'Accept: application/rdf+xml' 'https://scigraph.springernature.com/pub.10.1038/nmicrobiol.2016.246'


     

    This table displays all metadata directly associated to this object as RDF triples.

    294 TRIPLES      21 PREDICATES      71 URIs      21 LITERALS      9 BLANK NODES

    Subject Predicate Object
    1 sg:pub.10.1038/nmicrobiol.2016.246 schema:about anzsrc-for:11
    2 anzsrc-for:1107
    3 schema:author N416bd786bda1470eb19a53d4755a0a33
    4 schema:citation sg:pub.10.1007/bf01851332
    5 sg:pub.10.1007/bf02905027
    6 sg:pub.10.1007/s10545-010-9081-y
    7 sg:pub.10.1038/cr.2015.68
    8 sg:pub.10.1038/labinvest.2013.53
    9 sg:pub.10.1038/nature05894
    10 sg:pub.10.1038/nature08097
    11 sg:pub.10.1038/nature11986
    12 sg:pub.10.1038/ni.2833
    13 sg:pub.10.1038/ni.2956
    14 sg:pub.10.1038/ni.3398
    15 sg:pub.10.1038/nri.2016.70
    16 sg:pub.10.1186/1471-2105-7-538
    17 https://app.dimensions.ai/details/publication/pub.1076688690
    18 https://doi.org/10.1002/eji.200636398
    19 https://doi.org/10.1016/j.cell.2016.05.035
    20 https://doi.org/10.1016/j.cmet.2014.12.005
    21 https://doi.org/10.1016/j.cmet.2016.06.004
    22 https://doi.org/10.1016/j.immuni.2015.02.005
    23 https://doi.org/10.1016/j.tcb.2013.11.008
    24 https://doi.org/10.1016/s0022-510x(97)05379-3
    25 https://doi.org/10.1016/s1074-7613(00)80119-3
    26 https://doi.org/10.1021/ja2070889
    27 https://doi.org/10.1073/pnas.0308496101
    28 https://doi.org/10.1074/jbc.m110.107854
    29 https://doi.org/10.1074/jbc.m113.454538
    30 https://doi.org/10.1074/jbc.m114.603589
    31 https://doi.org/10.1074/jbc.m115.662114
    32 https://doi.org/10.1085/jgp.8.6.519
    33 https://doi.org/10.1093/bioinformatics/19.2.185
    34 https://doi.org/10.1093/nar/gkv380
    35 https://doi.org/10.1093/nar/gng015
    36 https://doi.org/10.1093/nar/gni179
    37 https://doi.org/10.1152/ajpregu.00584.2012
    38 https://doi.org/10.1182/blood-2006-02-002477
    39 https://doi.org/10.1182/blood-2009-10-249540
    40 https://doi.org/10.1371/journal.pone.0097702
    41 https://doi.org/10.1373/clinchem.2006.078873
    42 https://doi.org/10.3389/fimmu.2014.00420
    43 https://doi.org/10.4049/jimmunol.0901698
    44 https://doi.org/10.4049/jimmunol.1003613
    45 https://doi.org/10.4049/jimmunol.1403045
    46 schema:datePublished 2017-03
    47 schema:datePublishedReg 2017-03-01
    48 schema:description Microbial stimuli such as lipopolysaccharide (LPS) induce robust metabolic rewiring in immune cells known as the Warburg effect. It is unknown whether this increase in glycolysis and decrease in oxidative phosphorylation (OXPHOS) is a general characteristic of monocytes that have encountered a pathogen. Using CD14<sup>+</sup> monocytes from healthy donors, we demonstrated that most microbial stimuli increased glycolysis, but that only stimulation of Toll-like receptor (TLR) 4 with LPS led to a decrease in OXPHOS. Instead, activation of other TLRs, such as TLR2 activation by Pam3CysSK4 (P3C), increased oxygen consumption and mitochondrial enzyme activity. Transcriptome and metabolome analysis of monocytes stimulated with P3C versus LPS confirmed the divergent metabolic responses between both stimuli, and revealed significant differences in the tricarboxylic acid cycle, OXPHOS and lipid metabolism pathways following stimulation of monocytes with P3C versus LPS. At a functional level, pharmacological inhibition of complex I of the mitochondrial electron transport chain diminished cytokine production and phagocytosis in P3C- but not LPS-stimulated monocytes. Thus, unlike LPS, complex microbial stimuli and the TLR2 ligand P3C induce a specific pattern of metabolic rewiring that involves upregulation of both glycolysis and OXPHOS, which enables activation of host defence mechanisms such as cytokine production and phagocytosis.
    49 schema:genre research_article
    50 schema:inLanguage en
    51 schema:isAccessibleForFree false
    52 schema:isPartOf N921e8efab6d94f97b51cb3fbc52ebbee
    53 Nb93531a6989046b5be771d2e4197367c
    54 sg:journal.1052984
    55 schema:name Microbial stimulation of different Toll-like receptor signalling pathways induces diverse metabolic programmes in human monocytes
    56 schema:pagination nmicrobiol2016246
    57 schema:productId N08ea32ade10a4a10870949d040fad43d
    58 N5b02b013885548a38402804088fef2af
    59 N6fe2945c295342fa8b622307f264bebd
    60 N8ac4f5c1a0c544d2850c14cec15145da
    61 Nd5875a59a8b948a99c523d1f424a91d2
    62 schema:sameAs https://app.dimensions.ai/details/publication/pub.1006234853
    63 https://doi.org/10.1038/nmicrobiol.2016.246
    64 schema:sdDatePublished 2019-04-10T23:11
    65 schema:sdLicense https://scigraph.springernature.com/explorer/license/
    66 schema:sdPublisher Na6b9a086ef454ed5964a081726b0a75e
    67 schema:url http://www.nature.com/articles/nmicrobiol2016246
    68 sgo:license sg:explorer/license/
    69 sgo:sdDataset articles
    70 rdf:type schema:ScholarlyArticle
    71 N08ea32ade10a4a10870949d040fad43d schema:name dimensions_id
    72 schema:value pub.1006234853
    73 rdf:type schema:PropertyValue
    74 N2a257f2c2d9f479694613e56cdcddd64 rdf:first sg:person.014645240657.77
    75 rdf:rest Ne00a10b4b6984d2ba0607d6b0c94624a
    76 N31eee89bc81a42aeab9ab278be65aeb4 rdf:first sg:person.01263677437.18
    77 rdf:rest Na4b7fe2fb9e645b2afba80f5f8041802
    78 N416bd786bda1470eb19a53d4755a0a33 rdf:first sg:person.01074074465.58
    79 rdf:rest Nd4a13f631c894f0eb9367bfa8c6a7cd5
    80 N54196ff6ab5e4d10a7da684ec70c18b9 rdf:first sg:person.01021435034.00
    81 rdf:rest N31eee89bc81a42aeab9ab278be65aeb4
    82 N5a742958fb8e4cbc9e82db02fe2166c5 rdf:first sg:person.0607551400.36
    83 rdf:rest N54196ff6ab5e4d10a7da684ec70c18b9
    84 N5b02b013885548a38402804088fef2af schema:name pubmed_id
    85 schema:value 27991883
    86 rdf:type schema:PropertyValue
    87 N6605f81741c54f50b281db0150df395a rdf:first sg:person.01054123502.11
    88 rdf:rest N2a257f2c2d9f479694613e56cdcddd64
    89 N6fe2945c295342fa8b622307f264bebd schema:name readcube_id
    90 schema:value 1db31b62dec457c71b4753c11f88cbe297be9df45d5e2a90936c265d20945a42
    91 rdf:type schema:PropertyValue
    92 N8ac4f5c1a0c544d2850c14cec15145da schema:name nlm_unique_id
    93 schema:value 101674869
    94 rdf:type schema:PropertyValue
    95 N921e8efab6d94f97b51cb3fbc52ebbee schema:issueNumber 3
    96 rdf:type schema:PublicationIssue
    97 N927e56019a964b98a3d4839a2d210c56 rdf:first sg:person.015557745415.11
    98 rdf:rest Nd79ba4b69f714664bff5e92505c2d3a5
    99 Na4b7fe2fb9e645b2afba80f5f8041802 rdf:first sg:person.01010523164.38
    100 rdf:rest rdf:nil
    101 Na6b9a086ef454ed5964a081726b0a75e schema:name Springer Nature - SN SciGraph project
    102 rdf:type schema:Organization
    103 Nb93531a6989046b5be771d2e4197367c schema:volumeNumber 2
    104 rdf:type schema:PublicationVolume
    105 Nbd35b22891814f8086c2479956f073aa rdf:first sg:person.01143155310.36
    106 rdf:rest N5a742958fb8e4cbc9e82db02fe2166c5
    107 Nd4a13f631c894f0eb9367bfa8c6a7cd5 rdf:first sg:person.0611166036.68
    108 rdf:rest N927e56019a964b98a3d4839a2d210c56
    109 Nd5875a59a8b948a99c523d1f424a91d2 schema:name doi
    110 schema:value 10.1038/nmicrobiol.2016.246
    111 rdf:type schema:PropertyValue
    112 Nd79ba4b69f714664bff5e92505c2d3a5 rdf:first sg:person.01252630204.02
    113 rdf:rest N6605f81741c54f50b281db0150df395a
    114 Ne00a10b4b6984d2ba0607d6b0c94624a rdf:first sg:person.013350644377.65
    115 rdf:rest Nbd35b22891814f8086c2479956f073aa
    116 anzsrc-for:11 schema:inDefinedTermSet anzsrc-for:
    117 schema:name Medical and Health Sciences
    118 rdf:type schema:DefinedTerm
    119 anzsrc-for:1107 schema:inDefinedTermSet anzsrc-for:
    120 schema:name Immunology
    121 rdf:type schema:DefinedTerm
    122 sg:grant.3797303 http://pending.schema.org/fundedItem sg:pub.10.1038/nmicrobiol.2016.246
    123 rdf:type schema:MonetaryGrant
    124 sg:journal.1052984 schema:issn 2058-5276
    125 schema:name Nature Microbiology
    126 rdf:type schema:Periodical
    127 sg:person.01010523164.38 schema:affiliation https://www.grid.ac/institutes/grid.4818.5
    128 schema:familyName Stienstra
    129 schema:givenName Rinke
    130 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01010523164.38
    131 rdf:type schema:Person
    132 sg:person.01021435034.00 schema:affiliation https://www.grid.ac/institutes/grid.10417.33
    133 schema:familyName van Crevel
    134 schema:givenName Reinout
    135 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01021435034.00
    136 rdf:type schema:Person
    137 sg:person.01054123502.11 schema:affiliation https://www.grid.ac/institutes/grid.4818.5
    138 schema:familyName Hooiveld
    139 schema:givenName Guido J.
    140 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01054123502.11
    141 rdf:type schema:Person
    142 sg:person.01074074465.58 schema:affiliation https://www.grid.ac/institutes/grid.10417.33
    143 schema:familyName Lachmandas
    144 schema:givenName Ekta
    145 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01074074465.58
    146 rdf:type schema:Person
    147 sg:person.01143155310.36 schema:affiliation https://www.grid.ac/institutes/grid.10417.33
    148 schema:familyName Fransen
    149 schema:givenName Jack A. M.
    150 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01143155310.36
    151 rdf:type schema:Person
    152 sg:person.01252630204.02 schema:affiliation https://www.grid.ac/institutes/grid.10417.33
    153 schema:familyName Hijmans
    154 schema:givenName Anneke
    155 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01252630204.02
    156 rdf:type schema:Person
    157 sg:person.01263677437.18 schema:affiliation https://www.grid.ac/institutes/grid.10417.33
    158 schema:familyName Netea
    159 schema:givenName Mihai G.
    160 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01263677437.18
    161 rdf:type schema:Person
    162 sg:person.013350644377.65 schema:affiliation https://www.grid.ac/institutes/grid.10417.33
    163 schema:familyName Rodenburg
    164 schema:givenName Richard J.
    165 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.013350644377.65
    166 rdf:type schema:Person
    167 sg:person.014645240657.77 schema:affiliation https://www.grid.ac/institutes/grid.10417.33
    168 schema:familyName Joosten
    169 schema:givenName Leo A. B.
    170 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.014645240657.77
    171 rdf:type schema:Person
    172 sg:person.015557745415.11 schema:affiliation https://www.grid.ac/institutes/grid.4818.5
    173 schema:familyName Ratter
    174 schema:givenName Jacqueline M.
    175 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.015557745415.11
    176 rdf:type schema:Person
    177 sg:person.0607551400.36 schema:affiliation https://www.grid.ac/institutes/grid.5650.6
    178 schema:familyName Houtkooper
    179 schema:givenName Riekelt H.
    180 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0607551400.36
    181 rdf:type schema:Person
    182 sg:person.0611166036.68 schema:affiliation https://www.grid.ac/institutes/grid.4818.5
    183 schema:familyName Boutens
    184 schema:givenName Lily
    185 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0611166036.68
    186 rdf:type schema:Person
    187 sg:pub.10.1007/bf01851332 schema:sameAs https://app.dimensions.ai/details/publication/pub.1006918424
    188 https://doi.org/10.1007/bf01851332
    189 rdf:type schema:CreativeWork
    190 sg:pub.10.1007/bf02905027 schema:sameAs https://app.dimensions.ai/details/publication/pub.1080698775
    191 https://doi.org/10.1007/bf02905027
    192 rdf:type schema:CreativeWork
    193 sg:pub.10.1007/s10545-010-9081-y schema:sameAs https://app.dimensions.ai/details/publication/pub.1042592863
    194 https://doi.org/10.1007/s10545-010-9081-y
    195 rdf:type schema:CreativeWork
    196 sg:pub.10.1038/cr.2015.68 schema:sameAs https://app.dimensions.ai/details/publication/pub.1033519755
    197 https://doi.org/10.1038/cr.2015.68
    198 rdf:type schema:CreativeWork
    199 sg:pub.10.1038/labinvest.2013.53 schema:sameAs https://app.dimensions.ai/details/publication/pub.1001640730
    200 https://doi.org/10.1038/labinvest.2013.53
    201 rdf:type schema:CreativeWork
    202 sg:pub.10.1038/nature05894 schema:sameAs https://app.dimensions.ai/details/publication/pub.1050655831
    203 https://doi.org/10.1038/nature05894
    204 rdf:type schema:CreativeWork
    205 sg:pub.10.1038/nature08097 schema:sameAs https://app.dimensions.ai/details/publication/pub.1007048279
    206 https://doi.org/10.1038/nature08097
    207 rdf:type schema:CreativeWork
    208 sg:pub.10.1038/nature11986 schema:sameAs https://app.dimensions.ai/details/publication/pub.1051643661
    209 https://doi.org/10.1038/nature11986
    210 rdf:type schema:CreativeWork
    211 sg:pub.10.1038/ni.2833 schema:sameAs https://app.dimensions.ai/details/publication/pub.1027192784
    212 https://doi.org/10.1038/ni.2833
    213 rdf:type schema:CreativeWork
    214 sg:pub.10.1038/ni.2956 schema:sameAs https://app.dimensions.ai/details/publication/pub.1038049925
    215 https://doi.org/10.1038/ni.2956
    216 rdf:type schema:CreativeWork
    217 sg:pub.10.1038/ni.3398 schema:sameAs https://app.dimensions.ai/details/publication/pub.1043334409
    218 https://doi.org/10.1038/ni.3398
    219 rdf:type schema:CreativeWork
    220 sg:pub.10.1038/nri.2016.70 schema:sameAs https://app.dimensions.ai/details/publication/pub.1003163126
    221 https://doi.org/10.1038/nri.2016.70
    222 rdf:type schema:CreativeWork
    223 sg:pub.10.1186/1471-2105-7-538 schema:sameAs https://app.dimensions.ai/details/publication/pub.1034318296
    224 https://doi.org/10.1186/1471-2105-7-538
    225 rdf:type schema:CreativeWork
    226 https://app.dimensions.ai/details/publication/pub.1076688690 schema:CreativeWork
    227 https://doi.org/10.1002/eji.200636398 schema:sameAs https://app.dimensions.ai/details/publication/pub.1030199382
    228 rdf:type schema:CreativeWork
    229 https://doi.org/10.1016/j.cell.2016.05.035 schema:sameAs https://app.dimensions.ai/details/publication/pub.1048638138
    230 rdf:type schema:CreativeWork
    231 https://doi.org/10.1016/j.cmet.2014.12.005 schema:sameAs https://app.dimensions.ai/details/publication/pub.1021097318
    232 rdf:type schema:CreativeWork
    233 https://doi.org/10.1016/j.cmet.2016.06.004 schema:sameAs https://app.dimensions.ai/details/publication/pub.1050820088
    234 rdf:type schema:CreativeWork
    235 https://doi.org/10.1016/j.immuni.2015.02.005 schema:sameAs https://app.dimensions.ai/details/publication/pub.1046964949
    236 rdf:type schema:CreativeWork
    237 https://doi.org/10.1016/j.tcb.2013.11.008 schema:sameAs https://app.dimensions.ai/details/publication/pub.1036237735
    238 rdf:type schema:CreativeWork
    239 https://doi.org/10.1016/s0022-510x(97)05379-3 schema:sameAs https://app.dimensions.ai/details/publication/pub.1046435103
    240 rdf:type schema:CreativeWork
    241 https://doi.org/10.1016/s1074-7613(00)80119-3 schema:sameAs https://app.dimensions.ai/details/publication/pub.1022947328
    242 rdf:type schema:CreativeWork
    243 https://doi.org/10.1021/ja2070889 schema:sameAs https://app.dimensions.ai/details/publication/pub.1055850799
    244 rdf:type schema:CreativeWork
    245 https://doi.org/10.1073/pnas.0308496101 schema:sameAs https://app.dimensions.ai/details/publication/pub.1047153110
    246 rdf:type schema:CreativeWork
    247 https://doi.org/10.1074/jbc.m110.107854 schema:sameAs https://app.dimensions.ai/details/publication/pub.1006352899
    248 rdf:type schema:CreativeWork
    249 https://doi.org/10.1074/jbc.m113.454538 schema:sameAs https://app.dimensions.ai/details/publication/pub.1000333062
    250 rdf:type schema:CreativeWork
    251 https://doi.org/10.1074/jbc.m114.603589 schema:sameAs https://app.dimensions.ai/details/publication/pub.1045299996
    252 rdf:type schema:CreativeWork
    253 https://doi.org/10.1074/jbc.m115.662114 schema:sameAs https://app.dimensions.ai/details/publication/pub.1020882885
    254 rdf:type schema:CreativeWork
    255 https://doi.org/10.1085/jgp.8.6.519 schema:sameAs https://app.dimensions.ai/details/publication/pub.1031385086
    256 rdf:type schema:CreativeWork
    257 https://doi.org/10.1093/bioinformatics/19.2.185 schema:sameAs https://app.dimensions.ai/details/publication/pub.1011853799
    258 rdf:type schema:CreativeWork
    259 https://doi.org/10.1093/nar/gkv380 schema:sameAs https://app.dimensions.ai/details/publication/pub.1047923881
    260 rdf:type schema:CreativeWork
    261 https://doi.org/10.1093/nar/gng015 schema:sameAs https://app.dimensions.ai/details/publication/pub.1018638362
    262 rdf:type schema:CreativeWork
    263 https://doi.org/10.1093/nar/gni179 schema:sameAs https://app.dimensions.ai/details/publication/pub.1040526112
    264 rdf:type schema:CreativeWork
    265 https://doi.org/10.1152/ajpregu.00584.2012 schema:sameAs https://app.dimensions.ai/details/publication/pub.1049140409
    266 rdf:type schema:CreativeWork
    267 https://doi.org/10.1182/blood-2006-02-002477 schema:sameAs https://app.dimensions.ai/details/publication/pub.1046435094
    268 rdf:type schema:CreativeWork
    269 https://doi.org/10.1182/blood-2009-10-249540 schema:sameAs https://app.dimensions.ai/details/publication/pub.1030672391
    270 rdf:type schema:CreativeWork
    271 https://doi.org/10.1371/journal.pone.0097702 schema:sameAs https://app.dimensions.ai/details/publication/pub.1034064364
    272 rdf:type schema:CreativeWork
    273 https://doi.org/10.1373/clinchem.2006.078873 schema:sameAs https://app.dimensions.ai/details/publication/pub.1014549350
    274 rdf:type schema:CreativeWork
    275 https://doi.org/10.3389/fimmu.2014.00420 schema:sameAs https://app.dimensions.ai/details/publication/pub.1042494326
    276 rdf:type schema:CreativeWork
    277 https://doi.org/10.4049/jimmunol.0901698 schema:sameAs https://app.dimensions.ai/details/publication/pub.1005113830
    278 rdf:type schema:CreativeWork
    279 https://doi.org/10.4049/jimmunol.1003613 schema:sameAs https://app.dimensions.ai/details/publication/pub.1053705985
    280 rdf:type schema:CreativeWork
    281 https://doi.org/10.4049/jimmunol.1403045 schema:sameAs https://app.dimensions.ai/details/publication/pub.1079122929
    282 rdf:type schema:CreativeWork
    283 https://www.grid.ac/institutes/grid.10417.33 schema:alternateName Radboud University Nijmegen Medical Centre
    284 schema:name Department of Cell Biology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, 1105 AZ, Nijmegen, The Netherlands
    285 Department of Internal Medicine and Radboud Center for Infectious Diseases, Radboud University Medical Center, 6525 GA, Nijmegen, The Netherlands
    286 Department of Pediatrics, Radboud Center for Mitochondrial Medicine, 774 Translational Metabolic Laboratory, Radboud University Medical Center, 6525 GA, Nijmegen, The Netherlands
    287 rdf:type schema:Organization
    288 https://www.grid.ac/institutes/grid.4818.5 schema:alternateName Wageningen University & Research
    289 schema:name Department of Internal Medicine and Radboud Center for Infectious Diseases, Radboud University Medical Center, 6525 GA, Nijmegen, The Netherlands
    290 Nutrition, Metabolism and Genomics Group, Division of Human Nutrition, Wageningen University, 6708 WE, Wageningen, The Netherlands
    291 rdf:type schema:Organization
    292 https://www.grid.ac/institutes/grid.5650.6 schema:alternateName Academic Medical Center
    293 schema:name Laboratory Genetic Metabolic Diseases, Academic Medical Center, 1105 AZ, Amsterdam, The Netherlands
    294 rdf:type schema:Organization
     




    Preview window. Press ESC to close (or click here)


    ...