RapamycinFungusV1, Main, Exploration, bibRecord, 000D72

mTOR- and HIF-1α-mediated aerobic glycolysis as metabolic basis for trained immunity.

Identifieur interne : 000D72 ( Main/Exploration ); précédent : 000D71; suivant : 000D73

mTOR- and HIF-1α-mediated aerobic glycolysis as metabolic basis for trained immunity.

Auteurs : Shih-Chin Cheng [Pays-Bas] ; Jessica Quintin [Pays-Bas] ; Robert A. Cramer [États-Unis] ; Kelly M. Shepardson [États-Unis] ; Sadia Saeed [Pays-Bas] ; Vinod Kumar [Pays-Bas] ; Evangelos J. Giamarellos-Bourboulis [Grèce] ; Joost H A. Martens [Pays-Bas] ; Nagesha Appukudige Rao [Pays-Bas] ; Ali Aghajanirefah [Pays-Bas] ; Ganesh R. Manjeri [Pays-Bas] ; Yang Li [Pays-Bas] ; Daniela C. Ifrim [Pays-Bas] ; Rob J W. Arts [Pays-Bas] ; Brian M J W. Van Der Veer [Pays-Bas] ; Brian M J W. Van Der Meer [Pays-Bas] ; Peter M T. Deen [Pays-Bas] ; Colin Logie [Pays-Bas] ; Luke A. O'Neill [Irlande (pays)] ; Peter Willems [Pays-Bas] ; Frank L. Van De Veerdonk [Pays-Bas] ; Jos W M. Van Der Meer [Pays-Bas] ; Aylwin Ng [États-Unis] ; Leo A B. Joosten [Pays-Bas] ; Cisca Wijmenga [Pays-Bas] ; Hendrik G. Stunnenberg [Pays-Bas] ; Ramnik J. Xavier [États-Unis] ; Mihai G. Netea [Pays-Bas]

Source :

Science (New York, N.Y.) [ 1095-9203 ] ; 2014.

RBID : pubmed:25258083

Descripteurs français

English descriptors

KwdEn :
- Aerobiosis (immunology), Animals (MeSH), Candida albicans (immunology), Candidiasis (immunology), Candidiasis (metabolism), Disease Models, Animal (MeSH), Epigenesis, Genetic (MeSH), Female (MeSH), Glucose (metabolism), Glycolysis (immunology), Humans (MeSH), Hypoxia-Inducible Factor 1, alpha Subunit (genetics), Hypoxia-Inducible Factor 1, alpha Subunit (metabolism), Immunity, Innate (genetics), Immunologic Memory (genetics), Male (MeSH), Mice (MeSH), Mice, Inbred C57BL (MeSH), Monocytes (immunology), Monocytes (metabolism), Sepsis (genetics), Sepsis (immunology), Sepsis (metabolism), Staphylococcal Infections (immunology), Staphylococcal Infections (metabolism), Staphylococcus aureus (MeSH), TOR Serine-Threonine Kinases (genetics), TOR Serine-Threonine Kinases (metabolism), Transcriptome (MeSH), beta-Glucans (immunology).
MESH :
- chemical , genetics : Hypoxia-Inducible Factor 1, alpha Subunit, TOR Serine-Threonine Kinases.
- chemical , immunology : beta-Glucans.
- chemical , metabolism : Glucose, Hypoxia-Inducible Factor 1, alpha Subunit, TOR Serine-Threonine Kinases.
- genetics : Immunity, Innate, Immunologic Memory, Sepsis.
- immunology : Aerobiosis, Candida albicans, Candidiasis, Glycolysis, Monocytes, Sepsis, Staphylococcal Infections.
- metabolism : Candidiasis, Monocytes, Sepsis, Staphylococcal Infections.
- Animals, Disease Models, Animal, Epigenesis, Genetic, Female, Humans, Male, Mice, Mice, Inbred C57BL, Staphylococcus aureus, Transcriptome.

Abstract

Epigenetic reprogramming of myeloid cells, also known as trained immunity, confers nonspecific protection from secondary infections. Using histone modification profiles of human monocytes trained with the Candida albicans cell wall constituent β-glucan, together with a genome-wide transcriptome, we identified the induced expression of genes involved in glucose metabolism. Trained monocytes display high glucose consumption, high lactate production, and a high ratio of nicotinamide adenine dinucleotide (NAD(+)) to its reduced form (NADH), reflecting a shift in metabolism with an increase in glycolysis dependent on the activation of mammalian target of rapamycin (mTOR) through a dectin-1-Akt-HIF-1α (hypoxia-inducible factor-1α) pathway. Inhibition of Akt, mTOR, or HIF-1α blocked monocyte induction of trained immunity, whereas the adenosine monophosphate-activated protein kinase activator metformin inhibited the innate immune response to fungal infection. Mice with a myeloid cell-specific defect in HIF-1α were unable to mount trained immunity against bacterial sepsis. Our results indicate that induction of aerobic glycolysis through an Akt-mTOR-HIF-1α pathway represents the metabolic basis of trained immunity.

DOI: 10.1126/science.1250684
PubMed: 25258083
PubMed Central: PMC4226238

Affiliations:

Links toward previous steps (curation, corpus...)

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Le document en format XML

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<author><name sortKey="Arts, Rob J W" sort="Arts, Rob J W" uniqKey="Arts R" first="Rob J W" last="Arts">Rob J W. Arts</name>
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<author><name sortKey="Logie, Colin" sort="Logie, Colin" uniqKey="Logie C" first="Colin" last="Logie">Colin Logie</name>
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<author><name sortKey="O Neill, Luke A" sort="O Neill, Luke A" uniqKey="O Neill L" first="Luke A" last="O'Neill">Luke A. O'Neill</name>
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<author><name sortKey="Willems, Peter" sort="Willems, Peter" uniqKey="Willems P" first="Peter" last="Willems">Peter Willems</name>
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<country xml:lang="fr">Pays-Bas</country>
<wicri:regionArea>Department of Biochemistry, Faculties of Science and Medicine, Nijmegen Centre for Molecular Life Sciences, Radboud University, 6500 HB Nijmegen</wicri:regionArea>
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<author><name sortKey="Van Der Meer, Jos W M" sort="Van Der Meer, Jos W M" uniqKey="Van Der Meer J" first="Jos W M" last="Van Der Meer">Jos W M. Van Der Meer</name>
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<country xml:lang="fr">Pays-Bas</country>
<wicri:regionArea>Department of Internal Medicine, Radboud University Medical Center, 6525 GA Nijmegen</wicri:regionArea>
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</affiliation>
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<author><name sortKey="Ng, Aylwin" sort="Ng, Aylwin" uniqKey="Ng A" first="Aylwin" last="Ng">Aylwin Ng</name>
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<country xml:lang="fr">États-Unis</country>
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</placeName>
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<author><name sortKey="Joosten, Leo A B" sort="Joosten, Leo A B" uniqKey="Joosten L" first="Leo A B" last="Joosten">Leo A B. Joosten</name>
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<country xml:lang="fr">Pays-Bas</country>
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<author><name sortKey="Wijmenga, Cisca" sort="Wijmenga, Cisca" uniqKey="Wijmenga C" first="Cisca" last="Wijmenga">Cisca Wijmenga</name>
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<author><name sortKey="Xavier, Ramnik J" sort="Xavier, Ramnik J" uniqKey="Xavier R" first="Ramnik J" last="Xavier">Ramnik J. Xavier</name>
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<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Center for Computational and Integrative Biology and Gastrointestinal Unit, Massachusetts General Hospital, Harvard School of Medicine, Boston, MA 02114, USA. Broad Institute of MIT and Harvard, Cambridge, MA 02142</wicri:regionArea>
<placeName><region type="state">Massachusetts</region>
</placeName>
</affiliation>
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<author><name sortKey="Netea, Mihai G" sort="Netea, Mihai G" uniqKey="Netea M" first="Mihai G" last="Netea">Mihai G. Netea</name>
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<sourceDesc><biblStruct><analytic><title xml:lang="en">mTOR- and HIF-1α-mediated aerobic glycolysis as metabolic basis for trained immunity.</title>
<author><name sortKey="Cheng, Shih Chin" sort="Cheng, Shih Chin" uniqKey="Cheng S" first="Shih-Chin" last="Cheng">Shih-Chin Cheng</name>
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<author><name sortKey="Quintin, Jessica" sort="Quintin, Jessica" uniqKey="Quintin J" first="Jessica" last="Quintin">Jessica Quintin</name>
<affiliation wicri:level="1"><nlm:affiliation>Department of Internal Medicine, Radboud University Medical Center, 6525 GA Nijmegen, Netherlands.</nlm:affiliation>
<country xml:lang="fr">Pays-Bas</country>
<wicri:regionArea>Department of Internal Medicine, Radboud University Medical Center, 6525 GA Nijmegen</wicri:regionArea>
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</affiliation>
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<author><name sortKey="Cramer, Robert A" sort="Cramer, Robert A" uniqKey="Cramer R" first="Robert A" last="Cramer">Robert A. Cramer</name>
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<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Microbiology and Immunology, Geisel School of Medicine at Dartmouth, Hanover, NH 03755</wicri:regionArea>
<placeName><region type="state">New Hampshire</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Shepardson, Kelly M" sort="Shepardson, Kelly M" uniqKey="Shepardson K" first="Kelly M" last="Shepardson">Kelly M. Shepardson</name>
<affiliation wicri:level="2"><nlm:affiliation>Department of Microbiology and Immunology, Geisel School of Medicine at Dartmouth, Hanover, NH 03755, USA.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Microbiology and Immunology, Geisel School of Medicine at Dartmouth, Hanover, NH 03755</wicri:regionArea>
<placeName><region type="state">New Hampshire</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Saeed, Sadia" sort="Saeed, Sadia" uniqKey="Saeed S" first="Sadia" last="Saeed">Sadia Saeed</name>
<affiliation wicri:level="1"><nlm:affiliation>Department of Molecular Biology, Faculties of Science and Medicine, Nijmegen Centre for Molecular Life Sciences, Radboud University, 6500 HB Nijmegen, Netherlands.</nlm:affiliation>
<country xml:lang="fr">Pays-Bas</country>
<wicri:regionArea>Department of Molecular Biology, Faculties of Science and Medicine, Nijmegen Centre for Molecular Life Sciences, Radboud University, 6500 HB Nijmegen</wicri:regionArea>
<wicri:noRegion>6500 HB Nijmegen</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Kumar, Vinod" sort="Kumar, Vinod" uniqKey="Kumar V" first="Vinod" last="Kumar">Vinod Kumar</name>
<affiliation wicri:level="4"><nlm:affiliation>Department of Genetics, University of Groningen, University Medical Center Groningen, Groningen, Netherlands.</nlm:affiliation>
<country xml:lang="fr">Pays-Bas</country>
<wicri:regionArea>Department of Genetics, University of Groningen, University Medical Center Groningen, Groningen</wicri:regionArea>
<placeName><settlement type="city">Groningue</settlement>
<region nuts="2" type="province">Groningue (province)</region>
</placeName>
<orgName type="university">Université de Groningue</orgName>
</affiliation>
</author>
<author><name sortKey="Giamarellos Bourboulis, Evangelos J" sort="Giamarellos Bourboulis, Evangelos J" uniqKey="Giamarellos Bourboulis E" first="Evangelos J" last="Giamarellos-Bourboulis">Evangelos J. Giamarellos-Bourboulis</name>
<affiliation wicri:level="1"><nlm:affiliation>4th Department of Internal Medicine, University of Athens Medical School, 12462 Athens, Greece.</nlm:affiliation>
<country xml:lang="fr">Grèce</country>
<wicri:regionArea>4th Department of Internal Medicine, University of Athens Medical School, 12462 Athens</wicri:regionArea>
<placeName><settlement type="city">Athènes</settlement>
<region nuts="2" type="region">Attique (région)</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Martens, Joost H A" sort="Martens, Joost H A" uniqKey="Martens J" first="Joost H A" last="Martens">Joost H A. Martens</name>
<affiliation wicri:level="1"><nlm:affiliation>Department of Molecular Biology, Faculties of Science and Medicine, Nijmegen Centre for Molecular Life Sciences, Radboud University, 6500 HB Nijmegen, Netherlands.</nlm:affiliation>
<country xml:lang="fr">Pays-Bas</country>
<wicri:regionArea>Department of Molecular Biology, Faculties of Science and Medicine, Nijmegen Centre for Molecular Life Sciences, Radboud University, 6500 HB Nijmegen</wicri:regionArea>
<wicri:noRegion>6500 HB Nijmegen</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Rao, Nagesha Appukudige" sort="Rao, Nagesha Appukudige" uniqKey="Rao N" first="Nagesha Appukudige" last="Rao">Nagesha Appukudige Rao</name>
<affiliation wicri:level="1"><nlm:affiliation>Department of Molecular Biology, Faculties of Science and Medicine, Nijmegen Centre for Molecular Life Sciences, Radboud University, 6500 HB Nijmegen, Netherlands.</nlm:affiliation>
<country xml:lang="fr">Pays-Bas</country>
<wicri:regionArea>Department of Molecular Biology, Faculties of Science and Medicine, Nijmegen Centre for Molecular Life Sciences, Radboud University, 6500 HB Nijmegen</wicri:regionArea>
<wicri:noRegion>6500 HB Nijmegen</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Aghajanirefah, Ali" sort="Aghajanirefah, Ali" uniqKey="Aghajanirefah A" first="Ali" last="Aghajanirefah">Ali Aghajanirefah</name>
<affiliation wicri:level="1"><nlm:affiliation>Department of Molecular Biology, Faculties of Science and Medicine, Nijmegen Centre for Molecular Life Sciences, Radboud University, 6500 HB Nijmegen, Netherlands.</nlm:affiliation>
<country xml:lang="fr">Pays-Bas</country>
<wicri:regionArea>Department of Molecular Biology, Faculties of Science and Medicine, Nijmegen Centre for Molecular Life Sciences, Radboud University, 6500 HB Nijmegen</wicri:regionArea>
<wicri:noRegion>6500 HB Nijmegen</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Manjeri, Ganesh R" sort="Manjeri, Ganesh R" uniqKey="Manjeri G" first="Ganesh R" last="Manjeri">Ganesh R. Manjeri</name>
<affiliation wicri:level="1"><nlm:affiliation>Department of Biochemistry, Faculties of Science and Medicine, Nijmegen Centre for Molecular Life Sciences, Radboud University, 6500 HB Nijmegen, Netherlands.</nlm:affiliation>
<country xml:lang="fr">Pays-Bas</country>
<wicri:regionArea>Department of Biochemistry, Faculties of Science and Medicine, Nijmegen Centre for Molecular Life Sciences, Radboud University, 6500 HB Nijmegen</wicri:regionArea>
<wicri:noRegion>6500 HB Nijmegen</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Li, Yang" sort="Li, Yang" uniqKey="Li Y" first="Yang" last="Li">Yang Li</name>
<affiliation wicri:level="4"><nlm:affiliation>Department of Genetics, University of Groningen, University Medical Center Groningen, Groningen, Netherlands.</nlm:affiliation>
<country xml:lang="fr">Pays-Bas</country>
<wicri:regionArea>Department of Genetics, University of Groningen, University Medical Center Groningen, Groningen</wicri:regionArea>
<placeName><settlement type="city">Groningue</settlement>
<region nuts="2" type="province">Groningue (province)</region>
</placeName>
<orgName type="university">Université de Groningue</orgName>
</affiliation>
</author>
<author><name sortKey="Ifrim, Daniela C" sort="Ifrim, Daniela C" uniqKey="Ifrim D" first="Daniela C" last="Ifrim">Daniela C. Ifrim</name>
<affiliation wicri:level="1"><nlm:affiliation>Department of Internal Medicine, Radboud University Medical Center, 6525 GA Nijmegen, Netherlands.</nlm:affiliation>
<country xml:lang="fr">Pays-Bas</country>
<wicri:regionArea>Department of Internal Medicine, Radboud University Medical Center, 6525 GA Nijmegen</wicri:regionArea>
<wicri:noRegion>6525 GA Nijmegen</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Arts, Rob J W" sort="Arts, Rob J W" uniqKey="Arts R" first="Rob J W" last="Arts">Rob J W. Arts</name>
<affiliation wicri:level="1"><nlm:affiliation>Department of Internal Medicine, Radboud University Medical Center, 6525 GA Nijmegen, Netherlands.</nlm:affiliation>
<country xml:lang="fr">Pays-Bas</country>
<wicri:regionArea>Department of Internal Medicine, Radboud University Medical Center, 6525 GA Nijmegen</wicri:regionArea>
<wicri:noRegion>6525 GA Nijmegen</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Van Der Veer, Brian M J W" sort="Van Der Veer, Brian M J W" uniqKey="Van Der Veer B" first="Brian M J W" last="Van Der Veer">Brian M J W. Van Der Veer</name>
<affiliation wicri:level="1"><nlm:affiliation>Department of Molecular Biology, Faculties of Science and Medicine, Nijmegen Centre for Molecular Life Sciences, Radboud University, 6500 HB Nijmegen, Netherlands.</nlm:affiliation>
<country xml:lang="fr">Pays-Bas</country>
<wicri:regionArea>Department of Molecular Biology, Faculties of Science and Medicine, Nijmegen Centre for Molecular Life Sciences, Radboud University, 6500 HB Nijmegen</wicri:regionArea>
<wicri:noRegion>6500 HB Nijmegen</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Van Der Meer, Brian M J W" sort="Van Der Meer, Brian M J W" uniqKey="Van Der Meer B" first="Brian M J W" last="Van Der Meer">Brian M J W. Van Der Meer</name>
<affiliation wicri:level="4"><nlm:affiliation>Department of Genetics, University of Groningen, University Medical Center Groningen, Groningen, Netherlands.</nlm:affiliation>
<country xml:lang="fr">Pays-Bas</country>
<wicri:regionArea>Department of Genetics, University of Groningen, University Medical Center Groningen, Groningen</wicri:regionArea>
<placeName><settlement type="city">Groningue</settlement>
<region nuts="2" type="province">Groningue (province)</region>
</placeName>
<orgName type="university">Université de Groningue</orgName>
</affiliation>
</author>
<author><name sortKey="Deen, Peter M T" sort="Deen, Peter M T" uniqKey="Deen P" first="Peter M T" last="Deen">Peter M T. Deen</name>
<affiliation wicri:level="1"><nlm:affiliation>Department of Physiology, Radboud University Medical Center, 6525 GA Nijmegen, Netherlands.</nlm:affiliation>
<country xml:lang="fr">Pays-Bas</country>
<wicri:regionArea>Department of Physiology, Radboud University Medical Center, 6525 GA Nijmegen</wicri:regionArea>
<wicri:noRegion>6525 GA Nijmegen</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Logie, Colin" sort="Logie, Colin" uniqKey="Logie C" first="Colin" last="Logie">Colin Logie</name>
<affiliation wicri:level="1"><nlm:affiliation>Department of Molecular Biology, Faculties of Science and Medicine, Nijmegen Centre for Molecular Life Sciences, Radboud University, 6500 HB Nijmegen, Netherlands.</nlm:affiliation>
<country xml:lang="fr">Pays-Bas</country>
<wicri:regionArea>Department of Molecular Biology, Faculties of Science and Medicine, Nijmegen Centre for Molecular Life Sciences, Radboud University, 6500 HB Nijmegen</wicri:regionArea>
<wicri:noRegion>6500 HB Nijmegen</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="O Neill, Luke A" sort="O Neill, Luke A" uniqKey="O Neill L" first="Luke A" last="O'Neill">Luke A. O'Neill</name>
<affiliation wicri:level="1"><nlm:affiliation>School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin 2, Ireland.</nlm:affiliation>
<country xml:lang="fr">Irlande (pays)</country>
<wicri:regionArea>School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin 2</wicri:regionArea>
<wicri:noRegion>Dublin 2</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Willems, Peter" sort="Willems, Peter" uniqKey="Willems P" first="Peter" last="Willems">Peter Willems</name>
<affiliation wicri:level="1"><nlm:affiliation>Department of Biochemistry, Faculties of Science and Medicine, Nijmegen Centre for Molecular Life Sciences, Radboud University, 6500 HB Nijmegen, Netherlands.</nlm:affiliation>
<country xml:lang="fr">Pays-Bas</country>
<wicri:regionArea>Department of Biochemistry, Faculties of Science and Medicine, Nijmegen Centre for Molecular Life Sciences, Radboud University, 6500 HB Nijmegen</wicri:regionArea>
<wicri:noRegion>6500 HB Nijmegen</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Van De Veerdonk, Frank L" sort="Van De Veerdonk, Frank L" uniqKey="Van De Veerdonk F" first="Frank L" last="Van De Veerdonk">Frank L. Van De Veerdonk</name>
<affiliation wicri:level="1"><nlm:affiliation>Department of Internal Medicine, Radboud University Medical Center, 6525 GA Nijmegen, Netherlands.</nlm:affiliation>
<country xml:lang="fr">Pays-Bas</country>
<wicri:regionArea>Department of Internal Medicine, Radboud University Medical Center, 6525 GA Nijmegen</wicri:regionArea>
<wicri:noRegion>6525 GA Nijmegen</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Van Der Meer, Jos W M" sort="Van Der Meer, Jos W M" uniqKey="Van Der Meer J" first="Jos W M" last="Van Der Meer">Jos W M. Van Der Meer</name>
<affiliation wicri:level="1"><nlm:affiliation>Department of Internal Medicine, Radboud University Medical Center, 6525 GA Nijmegen, Netherlands.</nlm:affiliation>
<country xml:lang="fr">Pays-Bas</country>
<wicri:regionArea>Department of Internal Medicine, Radboud University Medical Center, 6525 GA Nijmegen</wicri:regionArea>
<wicri:noRegion>6525 GA Nijmegen</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Ng, Aylwin" sort="Ng, Aylwin" uniqKey="Ng A" first="Aylwin" last="Ng">Aylwin Ng</name>
<affiliation wicri:level="2"><nlm:affiliation>Center for Computational and Integrative Biology and Gastrointestinal Unit, Massachusetts General Hospital, Harvard School of Medicine, Boston, MA 02114, USA. Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Center for Computational and Integrative Biology and Gastrointestinal Unit, Massachusetts General Hospital, Harvard School of Medicine, Boston, MA 02114, USA. Broad Institute of MIT and Harvard, Cambridge, MA 02142</wicri:regionArea>
<placeName><region type="state">Massachusetts</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Joosten, Leo A B" sort="Joosten, Leo A B" uniqKey="Joosten L" first="Leo A B" last="Joosten">Leo A B. Joosten</name>
<affiliation wicri:level="1"><nlm:affiliation>Department of Internal Medicine, Radboud University Medical Center, 6525 GA Nijmegen, Netherlands.</nlm:affiliation>
<country xml:lang="fr">Pays-Bas</country>
<wicri:regionArea>Department of Internal Medicine, Radboud University Medical Center, 6525 GA Nijmegen</wicri:regionArea>
<wicri:noRegion>6525 GA Nijmegen</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Wijmenga, Cisca" sort="Wijmenga, Cisca" uniqKey="Wijmenga C" first="Cisca" last="Wijmenga">Cisca Wijmenga</name>
<affiliation wicri:level="4"><nlm:affiliation>Department of Genetics, University of Groningen, University Medical Center Groningen, Groningen, Netherlands.</nlm:affiliation>
<country xml:lang="fr">Pays-Bas</country>
<wicri:regionArea>Department of Genetics, University of Groningen, University Medical Center Groningen, Groningen</wicri:regionArea>
<placeName><settlement type="city">Groningue</settlement>
<region nuts="2" type="province">Groningue (province)</region>
</placeName>
<orgName type="university">Université de Groningue</orgName>
</affiliation>
</author>
<author><name sortKey="Stunnenberg, Hendrik G" sort="Stunnenberg, Hendrik G" uniqKey="Stunnenberg H" first="Hendrik G" last="Stunnenberg">Hendrik G. Stunnenberg</name>
<affiliation wicri:level="4"><nlm:affiliation>Department of Genetics, University of Groningen, University Medical Center Groningen, Groningen, Netherlands.</nlm:affiliation>
<country xml:lang="fr">Pays-Bas</country>
<wicri:regionArea>Department of Genetics, University of Groningen, University Medical Center Groningen, Groningen</wicri:regionArea>
<placeName><settlement type="city">Groningue</settlement>
<region nuts="2" type="province">Groningue (province)</region>
</placeName>
<orgName type="university">Université de Groningue</orgName>
</affiliation>
</author>
<author><name sortKey="Xavier, Ramnik J" sort="Xavier, Ramnik J" uniqKey="Xavier R" first="Ramnik J" last="Xavier">Ramnik J. Xavier</name>
<affiliation wicri:level="2"><nlm:affiliation>Center for Computational and Integrative Biology and Gastrointestinal Unit, Massachusetts General Hospital, Harvard School of Medicine, Boston, MA 02114, USA. Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Center for Computational and Integrative Biology and Gastrointestinal Unit, Massachusetts General Hospital, Harvard School of Medicine, Boston, MA 02114, USA. Broad Institute of MIT and Harvard, Cambridge, MA 02142</wicri:regionArea>
<placeName><region type="state">Massachusetts</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Netea, Mihai G" sort="Netea, Mihai G" uniqKey="Netea M" first="Mihai G" last="Netea">Mihai G. Netea</name>
<affiliation wicri:level="1"><nlm:affiliation>Department of Internal Medicine, Radboud University Medical Center, 6525 GA Nijmegen, Netherlands. mihai.netea@radboudumc.nl.</nlm:affiliation>
<country xml:lang="fr">Pays-Bas</country>
<wicri:regionArea>Department of Internal Medicine, Radboud University Medical Center, 6525 GA Nijmegen</wicri:regionArea>
<wicri:noRegion>6525 GA Nijmegen</wicri:noRegion>
</affiliation>
</author>
</analytic>
<series><title level="j">Science (New York, N.Y.)</title>
<idno type="eISSN">1095-9203</idno>
<imprint><date when="2014" type="published">2014</date>
</imprint>
</series>
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<profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Aerobiosis (immunology)</term>
<term>Animals (MeSH)</term>
<term>Candida albicans (immunology)</term>
<term>Candidiasis (immunology)</term>
<term>Candidiasis (metabolism)</term>
<term>Disease Models, Animal (MeSH)</term>
<term>Epigenesis, Genetic (MeSH)</term>
<term>Female (MeSH)</term>
<term>Glucose (metabolism)</term>
<term>Glycolysis (immunology)</term>
<term>Humans (MeSH)</term>
<term>Hypoxia-Inducible Factor 1, alpha Subunit (genetics)</term>
<term>Hypoxia-Inducible Factor 1, alpha Subunit (metabolism)</term>
<term>Immunity, Innate (genetics)</term>
<term>Immunologic Memory (genetics)</term>
<term>Male (MeSH)</term>
<term>Mice (MeSH)</term>
<term>Mice, Inbred C57BL (MeSH)</term>
<term>Monocytes (immunology)</term>
<term>Monocytes (metabolism)</term>
<term>Sepsis (genetics)</term>
<term>Sepsis (immunology)</term>
<term>Sepsis (metabolism)</term>
<term>Staphylococcal Infections (immunology)</term>
<term>Staphylococcal Infections (metabolism)</term>
<term>Staphylococcus aureus (MeSH)</term>
<term>TOR Serine-Threonine Kinases (genetics)</term>
<term>TOR Serine-Threonine Kinases (metabolism)</term>
<term>Transcriptome (MeSH)</term>
<term>beta-Glucans (immunology)</term>
</keywords>
<keywords scheme="KwdFr" xml:lang="fr"><term>Animaux (MeSH)</term>
<term>Aérobiose (immunologie)</term>
<term>Candida albicans (immunologie)</term>
<term>Candidose (immunologie)</term>
<term>Candidose (métabolisme)</term>
<term>Femelle (MeSH)</term>
<term>Glucose (métabolisme)</term>
<term>Glycolyse (immunologie)</term>
<term>Humains (MeSH)</term>
<term>Immunité innée (génétique)</term>
<term>Infections à staphylocoques (immunologie)</term>
<term>Infections à staphylocoques (métabolisme)</term>
<term>Modèles animaux de maladie humaine (MeSH)</term>
<term>Monocytes (immunologie)</term>
<term>Monocytes (métabolisme)</term>
<term>Mâle (MeSH)</term>
<term>Mémoire immunologique (génétique)</term>
<term>Sepsie (génétique)</term>
<term>Sepsie (immunologie)</term>
<term>Sepsie (métabolisme)</term>
<term>Souris (MeSH)</term>
<term>Souris de lignée C57BL (MeSH)</term>
<term>Sous-unité alpha du facteur-1 induit par l'hypoxie (génétique)</term>
<term>Sous-unité alpha du facteur-1 induit par l'hypoxie (métabolisme)</term>
<term>Staphylococcus aureus (MeSH)</term>
<term>Sérine-thréonine kinases TOR (génétique)</term>
<term>Sérine-thréonine kinases TOR (métabolisme)</term>
<term>Transcriptome (MeSH)</term>
<term>bêta-Glucanes (immunologie)</term>
<term>Épigenèse génétique (MeSH)</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>Hypoxia-Inducible Factor 1, alpha Subunit</term>
<term>TOR Serine-Threonine Kinases</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="immunology" xml:lang="en"><term>beta-Glucans</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Glucose</term>
<term>Hypoxia-Inducible Factor 1, alpha Subunit</term>
<term>TOR Serine-Threonine Kinases</term>
</keywords>
<keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>Immunity, Innate</term>
<term>Immunologic Memory</term>
<term>Sepsis</term>
</keywords>
<keywords scheme="MESH" qualifier="génétique" xml:lang="fr"><term>Immunité innée</term>
<term>Mémoire immunologique</term>
<term>Sepsie</term>
<term>Sous-unité alpha du facteur-1 induit par l'hypoxie</term>
<term>Sérine-thréonine kinases TOR</term>
</keywords>
<keywords scheme="MESH" qualifier="immunologie" xml:lang="fr"><term>Aérobiose</term>
<term>Candida albicans</term>
<term>Candidose</term>
<term>Glycolyse</term>
<term>Infections à staphylocoques</term>
<term>Monocytes</term>
<term>Sepsie</term>
<term>bêta-Glucanes</term>
</keywords>
<keywords scheme="MESH" qualifier="immunology" xml:lang="en"><term>Aerobiosis</term>
<term>Candida albicans</term>
<term>Candidiasis</term>
<term>Glycolysis</term>
<term>Monocytes</term>
<term>Sepsis</term>
<term>Staphylococcal Infections</term>
</keywords>
<keywords scheme="MESH" qualifier="metabolism" xml:lang="en"><term>Candidiasis</term>
<term>Monocytes</term>
<term>Sepsis</term>
<term>Staphylococcal Infections</term>
</keywords>
<keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr"><term>Candidose</term>
<term>Glucose</term>
<term>Infections à staphylocoques</term>
<term>Monocytes</term>
<term>Sepsie</term>
<term>Sous-unité alpha du facteur-1 induit par l'hypoxie</term>
<term>Sérine-thréonine kinases TOR</term>
</keywords>
<keywords scheme="MESH" xml:lang="en"><term>Animals</term>
<term>Disease Models, Animal</term>
<term>Epigenesis, Genetic</term>
<term>Female</term>
<term>Humans</term>
<term>Male</term>
<term>Mice</term>
<term>Mice, Inbred C57BL</term>
<term>Staphylococcus aureus</term>
<term>Transcriptome</term>
</keywords>
<keywords scheme="MESH" xml:lang="fr"><term>Animaux</term>
<term>Femelle</term>
<term>Humains</term>
<term>Modèles animaux de maladie humaine</term>
<term>Mâle</term>
<term>Souris</term>
<term>Souris de lignée C57BL</term>
<term>Staphylococcus aureus</term>
<term>Transcriptome</term>
<term>Épigenèse génétique</term>
</keywords>
</textClass>
</profileDesc>
</teiHeader>
<front><div type="abstract" xml:lang="en">Epigenetic reprogramming of myeloid cells, also known as trained immunity, confers nonspecific protection from secondary infections. Using histone modification profiles of human monocytes trained with the Candida albicans cell wall constituent β-glucan, together with a genome-wide transcriptome, we identified the induced expression of genes involved in glucose metabolism. Trained monocytes display high glucose consumption, high lactate production, and a high ratio of nicotinamide adenine dinucleotide (NAD(+)) to its reduced form (NADH), reflecting a shift in metabolism with an increase in glycolysis dependent on the activation of mammalian target of rapamycin (mTOR) through a dectin-1-Akt-HIF-1α (hypoxia-inducible factor-1α) pathway. Inhibition of Akt, mTOR, or HIF-1α blocked monocyte induction of trained immunity, whereas the adenosine monophosphate-activated protein kinase activator metformin inhibited the innate immune response to fungal infection. Mice with a myeloid cell-specific defect in HIF-1α were unable to mount trained immunity against bacterial sepsis. Our results indicate that induction of aerobic glycolysis through an Akt-mTOR-HIF-1α pathway represents the metabolic basis of trained immunity. </div>
</front>
</TEI>
<pubmed><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">25258083</PMID>
<DateCompleted><Year>2014</Year>
<Month>10</Month>
<Day>23</Day>
</DateCompleted>
<DateRevised><Year>2018</Year>
<Month>11</Month>
<Day>13</Day>
</DateRevised>
<Article PubModel="Print"><Journal><ISSN IssnType="Electronic">1095-9203</ISSN>
<JournalIssue CitedMedium="Internet"><Volume>345</Volume>
<Issue>6204</Issue>
<PubDate><Year>2014</Year>
<Month>Sep</Month>
<Day>26</Day>
</PubDate>
</JournalIssue>
<Title>Science (New York, N.Y.)</Title>
<ISOAbbreviation>Science</ISOAbbreviation>
</Journal>
<ArticleTitle>mTOR- and HIF-1α-mediated aerobic glycolysis as metabolic basis for trained immunity.</ArticleTitle>
<Pagination><MedlinePgn>1250684</MedlinePgn>
</Pagination>
<ELocationID EIdType="doi" ValidYN="Y">10.1126/science.1250684</ELocationID>
<ELocationID EIdType="pii" ValidYN="Y">1250684</ELocationID>
<Abstract><AbstractText>Epigenetic reprogramming of myeloid cells, also known as trained immunity, confers nonspecific protection from secondary infections. Using histone modification profiles of human monocytes trained with the Candida albicans cell wall constituent β-glucan, together with a genome-wide transcriptome, we identified the induced expression of genes involved in glucose metabolism. Trained monocytes display high glucose consumption, high lactate production, and a high ratio of nicotinamide adenine dinucleotide (NAD(+)) to its reduced form (NADH), reflecting a shift in metabolism with an increase in glycolysis dependent on the activation of mammalian target of rapamycin (mTOR) through a dectin-1-Akt-HIF-1α (hypoxia-inducible factor-1α) pathway. Inhibition of Akt, mTOR, or HIF-1α blocked monocyte induction of trained immunity, whereas the adenosine monophosphate-activated protein kinase activator metformin inhibited the innate immune response to fungal infection. Mice with a myeloid cell-specific defect in HIF-1α were unable to mount trained immunity against bacterial sepsis. Our results indicate that induction of aerobic glycolysis through an Akt-mTOR-HIF-1α pathway represents the metabolic basis of trained immunity. </AbstractText>
<CopyrightInformation>Copyright © 2014, American Association for the Advancement of Science.</CopyrightInformation>
</Abstract>
<AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Cheng</LastName>
<ForeName>Shih-Chin</ForeName>
<Initials>SC</Initials>
<AffiliationInfo><Affiliation>Department of Internal Medicine, Radboud University Medical Center, 6525 GA Nijmegen, Netherlands.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Quintin</LastName>
<ForeName>Jessica</ForeName>
<Initials>J</Initials>
<AffiliationInfo><Affiliation>Department of Internal Medicine, Radboud University Medical Center, 6525 GA Nijmegen, Netherlands.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Cramer</LastName>
<ForeName>Robert A</ForeName>
<Initials>RA</Initials>
<AffiliationInfo><Affiliation>Department of Microbiology and Immunology, Geisel School of Medicine at Dartmouth, Hanover, NH 03755, USA.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Shepardson</LastName>
<ForeName>Kelly M</ForeName>
<Initials>KM</Initials>
<AffiliationInfo><Affiliation>Department of Microbiology and Immunology, Geisel School of Medicine at Dartmouth, Hanover, NH 03755, USA.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Saeed</LastName>
<ForeName>Sadia</ForeName>
<Initials>S</Initials>
<AffiliationInfo><Affiliation>Department of Molecular Biology, Faculties of Science and Medicine, Nijmegen Centre for Molecular Life Sciences, Radboud University, 6500 HB Nijmegen, Netherlands.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Kumar</LastName>
<ForeName>Vinod</ForeName>
<Initials>V</Initials>
<AffiliationInfo><Affiliation>Department of Genetics, University of Groningen, University Medical Center Groningen, Groningen, Netherlands.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Giamarellos-Bourboulis</LastName>
<ForeName>Evangelos J</ForeName>
<Initials>EJ</Initials>
<AffiliationInfo><Affiliation>4th Department of Internal Medicine, University of Athens Medical School, 12462 Athens, Greece.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Martens</LastName>
<ForeName>Joost H A</ForeName>
<Initials>JH</Initials>
<AffiliationInfo><Affiliation>Department of Molecular Biology, Faculties of Science and Medicine, Nijmegen Centre for Molecular Life Sciences, Radboud University, 6500 HB Nijmegen, Netherlands.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Rao</LastName>
<ForeName>Nagesha Appukudige</ForeName>
<Initials>NA</Initials>
<AffiliationInfo><Affiliation>Department of Molecular Biology, Faculties of Science and Medicine, Nijmegen Centre for Molecular Life Sciences, Radboud University, 6500 HB Nijmegen, Netherlands.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Aghajanirefah</LastName>
<ForeName>Ali</ForeName>
<Initials>A</Initials>
<AffiliationInfo><Affiliation>Department of Molecular Biology, Faculties of Science and Medicine, Nijmegen Centre for Molecular Life Sciences, Radboud University, 6500 HB Nijmegen, Netherlands.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Manjeri</LastName>
<ForeName>Ganesh R</ForeName>
<Initials>GR</Initials>
<AffiliationInfo><Affiliation>Department of Biochemistry, Faculties of Science and Medicine, Nijmegen Centre for Molecular Life Sciences, Radboud University, 6500 HB Nijmegen, Netherlands.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Li</LastName>
<ForeName>Yang</ForeName>
<Initials>Y</Initials>
<AffiliationInfo><Affiliation>Department of Genetics, University of Groningen, University Medical Center Groningen, Groningen, Netherlands.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Ifrim</LastName>
<ForeName>Daniela C</ForeName>
<Initials>DC</Initials>
<AffiliationInfo><Affiliation>Department of Internal Medicine, Radboud University Medical Center, 6525 GA Nijmegen, Netherlands.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Arts</LastName>
<ForeName>Rob J W</ForeName>
<Initials>RJ</Initials>
<AffiliationInfo><Affiliation>Department of Internal Medicine, Radboud University Medical Center, 6525 GA Nijmegen, Netherlands.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>van der Veer</LastName>
<ForeName>Brian M J W</ForeName>
<Initials>BM</Initials>
<AffiliationInfo><Affiliation>Department of Molecular Biology, Faculties of Science and Medicine, Nijmegen Centre for Molecular Life Sciences, Radboud University, 6500 HB Nijmegen, Netherlands.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="N"><LastName>van der Meer</LastName>
<ForeName>Brian M J W</ForeName>
<Initials>BM</Initials>
<AffiliationInfo><Affiliation>Department of Genetics, University of Groningen, University Medical Center Groningen, Groningen, Netherlands.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Deen</LastName>
<ForeName>Peter M T</ForeName>
<Initials>PM</Initials>
<AffiliationInfo><Affiliation>Department of Physiology, Radboud University Medical Center, 6525 GA Nijmegen, Netherlands.</Affiliation>
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<AffiliationInfo><Affiliation>Department of Molecular Biology, Faculties of Science and Medicine, Nijmegen Centre for Molecular Life Sciences, Radboud University, 6500 HB Nijmegen, Netherlands.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>O'Neill</LastName>
<ForeName>Luke A</ForeName>
<Initials>LA</Initials>
<AffiliationInfo><Affiliation>School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin 2, Ireland.</Affiliation>
</AffiliationInfo>
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<Author ValidYN="Y"><LastName>Willems</LastName>
<ForeName>Peter</ForeName>
<Initials>P</Initials>
<AffiliationInfo><Affiliation>Department of Biochemistry, Faculties of Science and Medicine, Nijmegen Centre for Molecular Life Sciences, Radboud University, 6500 HB Nijmegen, Netherlands.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>van de Veerdonk</LastName>
<ForeName>Frank L</ForeName>
<Initials>FL</Initials>
<AffiliationInfo><Affiliation>Department of Internal Medicine, Radboud University Medical Center, 6525 GA Nijmegen, Netherlands.</Affiliation>
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<Author ValidYN="Y"><LastName>van der Meer</LastName>
<ForeName>Jos W M</ForeName>
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<AffiliationInfo><Affiliation>Department of Internal Medicine, Radboud University Medical Center, 6525 GA Nijmegen, Netherlands.</Affiliation>
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<Author ValidYN="Y"><LastName>Ng</LastName>
<ForeName>Aylwin</ForeName>
<Initials>A</Initials>
<AffiliationInfo><Affiliation>Center for Computational and Integrative Biology and Gastrointestinal Unit, Massachusetts General Hospital, Harvard School of Medicine, Boston, MA 02114, USA. Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.</Affiliation>
</AffiliationInfo>
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<ForeName>Leo A B</ForeName>
<Initials>LA</Initials>
<AffiliationInfo><Affiliation>Department of Internal Medicine, Radboud University Medical Center, 6525 GA Nijmegen, Netherlands.</Affiliation>
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</Author>
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<ForeName>Cisca</ForeName>
<Initials>C</Initials>
<AffiliationInfo><Affiliation>Department of Genetics, University of Groningen, University Medical Center Groningen, Groningen, Netherlands.</Affiliation>
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<ForeName>Hendrik G</ForeName>
<Initials>HG</Initials>
<AffiliationInfo><Affiliation>Department of Genetics, University of Groningen, University Medical Center Groningen, Groningen, Netherlands.</Affiliation>
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<Author ValidYN="Y"><LastName>Xavier</LastName>
<ForeName>Ramnik J</ForeName>
<Initials>RJ</Initials>
<AffiliationInfo><Affiliation>Center for Computational and Integrative Biology and Gastrointestinal Unit, Massachusetts General Hospital, Harvard School of Medicine, Boston, MA 02114, USA. Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Netea</LastName>
<ForeName>Mihai G</ForeName>
<Initials>MG</Initials>
<AffiliationInfo><Affiliation>Department of Internal Medicine, Radboud University Medical Center, 6525 GA Nijmegen, Netherlands. mihai.netea@radboudumc.nl.</Affiliation>
</AffiliationInfo>
</Author>
</AuthorList>
<Language>eng</Language>
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<AccessionNumberList><AccessionNumber>GSE57206</AccessionNumber>
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<Acronym>GM</Acronym>
<Agency>NIGMS NIH HHS</Agency>
<Country>United States</Country>
</Grant>
<Grant><GrantID>P30 DK043351</GrantID>
<Acronym>DK</Acronym>
<Agency>NIDDK NIH HHS</Agency>
<Country>United States</Country>
</Grant>
<Grant><GrantID>P30 GM106394</GrantID>
<Acronym>GM</Acronym>
<Agency>NIGMS NIH HHS</Agency>
<Country>United States</Country>
</Grant>
<Grant><GrantID>R01 AI081838</GrantID>
<Acronym>AI</Acronym>
<Agency>NIAID NIH HHS</Agency>
<Country>United States</Country>
</Grant>
<Grant><GrantID>R01AI81838</GrantID>
<Acronym>AI</Acronym>
<Agency>NIAID NIH HHS</Agency>
<Country>United States</Country>
</Grant>
<Grant><GrantID>DK43351</GrantID>
<Acronym>DK</Acronym>
<Agency>NIDDK NIH HHS</Agency>
<Country>United States</Country>
</Grant>
<Grant><GrantID>P30 GM103415</GrantID>
<Acronym>GM</Acronym>
<Agency>NIGMS NIH HHS</Agency>
<Country>United States</Country>
</Grant>
<Grant><GrantID>310372</GrantID>
<Agency>European Research Council</Agency>
<Country>International</Country>
</Grant>
<Grant><GrantID>1P30GM106394-01</GrantID>
<Acronym>GM</Acronym>
<Agency>NIGMS NIH HHS</Agency>
<Country>United States</Country>
</Grant>
<Grant><GrantID>DK097485</GrantID>
<Acronym>DK</Acronym>
<Agency>NIDDK NIH HHS</Agency>
<Country>United States</Country>
</Grant>
<Grant><GrantID>R01 DK097485</GrantID>
<Acronym>DK</Acronym>
<Agency>NIDDK NIH HHS</Agency>
<Country>United States</Country>
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<NlmUniqueID>0404511</NlmUniqueID>
<ISSNLinking>0036-8075</ISSNLinking>
</MedlineJournalInfo>
<ChemicalList><Chemical><RegistryNumber>0</RegistryNumber>
<NameOfSubstance UI="C497443">Hif1a protein, mouse</NameOfSubstance>
</Chemical>
<Chemical><RegistryNumber>0</RegistryNumber>
<NameOfSubstance UI="D051795">Hypoxia-Inducible Factor 1, alpha Subunit</NameOfSubstance>
</Chemical>
<Chemical><RegistryNumber>0</RegistryNumber>
<NameOfSubstance UI="D047071">beta-Glucans</NameOfSubstance>
</Chemical>
<Chemical><RegistryNumber>EC 2.7.1.1</RegistryNumber>
<NameOfSubstance UI="D058570">TOR Serine-Threonine Kinases</NameOfSubstance>
</Chemical>
<Chemical><RegistryNumber>EC 2.7.1.1</RegistryNumber>
<NameOfSubstance UI="C546843">mTOR protein, mouse</NameOfSubstance>
</Chemical>
<Chemical><RegistryNumber>IY9XDZ35W2</RegistryNumber>
<NameOfSubstance UI="D005947">Glucose</NameOfSubstance>
</Chemical>
</ChemicalList>
<CitationSubset>IM</CitationSubset>
<CommentsCorrectionsList><CommentsCorrections RefType="ErratumIn"><RefSource>Science. 2014 Nov 7;346(6210):aaa1503</RefSource>
<Note>van der Meer, Brian M J W [corrected to van der Veer, Brian M J W]</Note>
</CommentsCorrections>
<CommentsCorrections RefType="CommentIn"><RefSource>Nat Rev Immunol. 2014 Nov;14(11):713</RefSource>
<PMID Version="1">25301255</PMID>
</CommentsCorrections>
</CommentsCorrectionsList>
<MeshHeadingList><MeshHeading><DescriptorName UI="D000332" MajorTopicYN="N">Aerobiosis</DescriptorName>
<QualifierName UI="Q000276" MajorTopicYN="N">immunology</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D000818" MajorTopicYN="N">Animals</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D002176" MajorTopicYN="N">Candida albicans</DescriptorName>
<QualifierName UI="Q000276" MajorTopicYN="N">immunology</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D002177" MajorTopicYN="N">Candidiasis</DescriptorName>
<QualifierName UI="Q000276" MajorTopicYN="N">immunology</QualifierName>
<QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D004195" MajorTopicYN="N">Disease Models, Animal</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D044127" MajorTopicYN="Y">Epigenesis, Genetic</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D005260" MajorTopicYN="N">Female</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D005947" MajorTopicYN="N">Glucose</DescriptorName>
<QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D006019" MajorTopicYN="N">Glycolysis</DescriptorName>
<QualifierName UI="Q000276" MajorTopicYN="Y">immunology</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D006801" MajorTopicYN="N">Humans</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D051795" MajorTopicYN="N">Hypoxia-Inducible Factor 1, alpha Subunit</DescriptorName>
<QualifierName UI="Q000235" MajorTopicYN="N">genetics</QualifierName>
<QualifierName UI="Q000378" MajorTopicYN="Y">metabolism</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D007113" MajorTopicYN="N">Immunity, Innate</DescriptorName>
<QualifierName UI="Q000235" MajorTopicYN="Y">genetics</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D007156" MajorTopicYN="N">Immunologic Memory</DescriptorName>
<QualifierName UI="Q000235" MajorTopicYN="Y">genetics</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D008297" MajorTopicYN="N">Male</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D051379" MajorTopicYN="N">Mice</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D008810" MajorTopicYN="N">Mice, Inbred C57BL</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D009000" MajorTopicYN="N">Monocytes</DescriptorName>
<QualifierName UI="Q000276" MajorTopicYN="Y">immunology</QualifierName>
<QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D018805" MajorTopicYN="N">Sepsis</DescriptorName>
<QualifierName UI="Q000235" MajorTopicYN="N">genetics</QualifierName>
<QualifierName UI="Q000276" MajorTopicYN="N">immunology</QualifierName>
<QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D013203" MajorTopicYN="N">Staphylococcal Infections</DescriptorName>
<QualifierName UI="Q000276" MajorTopicYN="N">immunology</QualifierName>
<QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D013211" MajorTopicYN="N">Staphylococcus aureus</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D058570" MajorTopicYN="N">TOR Serine-Threonine Kinases</DescriptorName>
<QualifierName UI="Q000235" MajorTopicYN="N">genetics</QualifierName>
<QualifierName UI="Q000378" MajorTopicYN="Y">metabolism</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D059467" MajorTopicYN="N">Transcriptome</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D047071" MajorTopicYN="N">beta-Glucans</DescriptorName>
<QualifierName UI="Q000276" MajorTopicYN="N">immunology</QualifierName>
</MeshHeading>
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	Serveur d'exploration sur la rapamycine et les champignons
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Serveur d'exploration sur la rapamycine et les champignons

mTOR- and HIF-1α-mediated aerobic glycolysis as metabolic basis for trained immunity.

mTOR- and HIF-1α-mediated aerobic glycolysis as metabolic basis for trained immunity.

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