RapamycinFungusV1, Main, Exploration, bibRecord, 000847

Fasting metabolism modulates the interleukin-12/interleukin-10 cytokine axis.

Identifieur interne : 000847 ( Main/Exploration ); précédent : 000846; suivant : 000848

Fasting metabolism modulates the interleukin-12/interleukin-10 cytokine axis.

Auteurs : Johannes J. Kovarik [Autriche] ; Elisabeth Kernbauer [Autriche] ; Markus A. Hölzl [Autriche] ; Johannes Hofer [Autriche] ; Guido A. Gualdoni [Autriche] ; Klaus G. Schmetterer [Autriche] ; Fitore Miftari [Autriche] ; Yury Sobanov [Autriche] ; Anastasia Meshcheryakova [Autriche] ; Diana Mechtcheriakova [Autriche] ; Nadine Witzeneder [Autriche] ; Georg Greiner [Autriche] ; Anna Ohradanova-Repic [Autriche] ; Petra Waidhofer-Söllner [Autriche] ; Marcus D. S Emann [Autriche] ; Thomas Decker [Autriche] ; Gerhard J. Zlabinger [Autriche]

Source :

PloS one [ 1932-6203 ] ; 2017.

RBID : pubmed:28742108

Descripteurs français

KwdFr :
- AMP-Activated Protein Kinases (métabolisme), Animaux (MeSH), Cellules cultivées (MeSH), Cellules myéloïdes (effets des médicaments et des substances chimiques), Cellules myéloïdes (immunologie), Cellules myéloïdes (métabolisme), Charge bactérienne (MeSH), Désoxyglucose (pharmacologie), Femelle (MeSH), Humains (MeSH), Infections à Listeria (immunologie), Infections à Listeria (microbiologie), Infections à Listeria (métabolisme), Interleukine-10 (métabolisme), Interleukine-12 (métabolisme), Jeûne (métabolisme), Modèles animaux de maladie humaine (MeSH), Métabolome (MeSH), Récepteurs de type Toll (métabolisme), Souris (MeSH), Souris de lignée BALB C (MeSH), Sérine-thréonine kinases TOR (métabolisme), Transduction du signal (MeSH).
MESH :
- effets des médicaments et des substances chimiques : Cellules myéloïdes.
- immunologie : Cellules myéloïdes, Infections à Listeria.
- microbiologie : Infections à Listeria.
- métabolisme : AMP-Activated Protein Kinases, Cellules myéloïdes, Infections à Listeria, Interleukine-10, Interleukine-12, Jeûne, Récepteurs de type Toll, Sérine-thréonine kinases TOR.
- pharmacologie : Désoxyglucose.
- Animaux, Cellules cultivées, Charge bactérienne, Femelle, Humains, Modèles animaux de maladie humaine, Métabolome, Souris, Souris de lignée BALB C, Transduction du signal.

English descriptors

KwdEn :
- AMP-Activated Protein Kinases (metabolism), Animals (MeSH), Bacterial Load (MeSH), Cells, Cultured (MeSH), Deoxyglucose (pharmacology), Disease Models, Animal (MeSH), Fasting (metabolism), Female (MeSH), Humans (MeSH), Interleukin-10 (metabolism), Interleukin-12 (metabolism), Listeriosis (immunology), Listeriosis (metabolism), Listeriosis (microbiology), Metabolome (MeSH), Mice (MeSH), Mice, Inbred BALB C (MeSH), Myeloid Cells (drug effects), Myeloid Cells (immunology), Myeloid Cells (metabolism), Signal Transduction (MeSH), TOR Serine-Threonine Kinases (metabolism), Toll-Like Receptors (metabolism).
MESH :
- chemical , metabolism : AMP-Activated Protein Kinases, Interleukin-10, Interleukin-12, TOR Serine-Threonine Kinases, Toll-Like Receptors.
- chemical , pharmacology : Deoxyglucose.
- drug effects : Myeloid Cells.
- immunology : Listeriosis, Myeloid Cells.
- metabolism : Fasting, Listeriosis, Myeloid Cells.
- microbiology : Listeriosis.
- Animals, Bacterial Load, Cells, Cultured, Disease Models, Animal, Female, Humans, Metabolome, Mice, Mice, Inbred BALB C, Signal Transduction.

Abstract

A crucial role of cell metabolism in immune cell differentiation and function has been recently established. Growing evidence indicates that metabolic processes impact both, innate and adaptive immunity. Since a down-stream integrator of metabolic alterations, mammalian target of rapamycin (mTOR), is responsible for controlling the balance between pro-inflammatory interleukin (IL)-12 and anti-inflammatory IL-10, we investigated the effect of upstream interference using metabolic modulators on the production of pro- and anti-inflammatory cytokines. Cytokine release and protein expression in human and murine myeloid cells was assessed after toll-like receptor (TLR)-activation and glucose-deprivation or co-treatment with 5'-adenosine monophosphate (AMP)-activated protein kinase (AMPK) activators. Additionally, the impact of metabolic interference was analysed in an in-vivo mouse model. Glucose-deprivation by 2-deoxy-D-glucose (2-DG) increased the production of IL-12p40 and IL-23p19 in monocytes, but dose-dependently inhibited the release of anti-inflammatory IL-10. Similar effects have been observed using pharmacological AMPK activation. Consistently, an inhibition of the tuberous sclerosis complex-mTOR pathway was observed. In line with our in vitro observations, glycolysis inhibition with 2-DG showed significantly reduced bacterial burden in a Th2-prone Listeria monocytogenes mouse infection model. In conclusion, we showed that fasting metabolism modulates the IL-12/IL-10 cytokine balance, establishing novel targets for metabolism-based immune-modulation.

DOI: 10.1371/journal.pone.0180900
PubMed: 28742108
PubMed Central: PMC5524343

Affiliations:

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Le document en format XML

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<author><name sortKey="Sobanov, Yury" sort="Sobanov, Yury" uniqKey="Sobanov Y" first="Yury" last="Sobanov">Yury Sobanov</name>
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<author><name sortKey="Meshcheryakova, Anastasia" sort="Meshcheryakova, Anastasia" uniqKey="Meshcheryakova A" first="Anastasia" last="Meshcheryakova">Anastasia Meshcheryakova</name>
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<wicri:regionArea>Department of Pathophysiology and Allergy Research, Center of Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna</wicri:regionArea>
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<author><name sortKey="Mechtcheriakova, Diana" sort="Mechtcheriakova, Diana" uniqKey="Mechtcheriakova D" first="Diana" last="Mechtcheriakova">Diana Mechtcheriakova</name>
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<wicri:regionArea>Department of Pathophysiology and Allergy Research, Center of Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna</wicri:regionArea>
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<author><name sortKey="Witzeneder, Nadine" sort="Witzeneder, Nadine" uniqKey="Witzeneder N" first="Nadine" last="Witzeneder">Nadine Witzeneder</name>
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<author><name sortKey="Greiner, Georg" sort="Greiner, Georg" uniqKey="Greiner G" first="Georg" last="Greiner">Georg Greiner</name>
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<author><name sortKey="Ohradanova Repic, Anna" sort="Ohradanova Repic, Anna" uniqKey="Ohradanova Repic A" first="Anna" last="Ohradanova-Repic">Anna Ohradanova-Repic</name>
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<country xml:lang="fr">Autriche</country>
<wicri:regionArea>Institute of Hygiene and Applied Immunology, Center of Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna</wicri:regionArea>
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<region nuts="2" type="province">Vienne (Autriche)</region>
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<author><name sortKey="Waidhofer Sollner, Petra" sort="Waidhofer Sollner, Petra" uniqKey="Waidhofer Sollner P" first="Petra" last="Waidhofer-Söllner">Petra Waidhofer-Söllner</name>
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<author><name sortKey="S Emann, Marcus D" sort="S Emann, Marcus D" uniqKey="S Emann M" first="Marcus D" last="S Emann">Marcus D. S Emann</name>
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<country xml:lang="fr">Autriche</country>
<wicri:regionArea>Department of Internal Medicine III, Clinical Division of Nephrology and Dialysis, Medical University Vienna, Vienna</wicri:regionArea>
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<author><name sortKey="Decker, Thomas" sort="Decker, Thomas" uniqKey="Decker T" first="Thomas" last="Decker">Thomas Decker</name>
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<country xml:lang="fr">Autriche</country>
<wicri:regionArea>Max F. Perutz Laboratories, Department of Microbiology and Immunobiology, University of Vienna, Vienna</wicri:regionArea>
<placeName><settlement type="city">Vienne (Autriche)</settlement>
<region nuts="2" type="province">Vienne (Autriche)</region>
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<author><name sortKey="Zlabinger, Gerhard J" sort="Zlabinger, Gerhard J" uniqKey="Zlabinger G" first="Gerhard J" last="Zlabinger">Gerhard J. Zlabinger</name>
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<country xml:lang="fr">Autriche</country>
<wicri:regionArea>Institute of Immunology, Center of Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna</wicri:regionArea>
<placeName><settlement type="city">Vienne (Autriche)</settlement>
<region nuts="2" type="province">Vienne (Autriche)</region>
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<sourceDesc><biblStruct><analytic><title xml:lang="en">Fasting metabolism modulates the interleukin-12/interleukin-10 cytokine axis.</title>
<author><name sortKey="Kovarik, Johannes J" sort="Kovarik, Johannes J" uniqKey="Kovarik J" first="Johannes J" last="Kovarik">Johannes J. Kovarik</name>
<affiliation wicri:level="3"><nlm:affiliation>Institute of Immunology, Center of Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria.</nlm:affiliation>
<country xml:lang="fr">Autriche</country>
<wicri:regionArea>Institute of Immunology, Center of Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna</wicri:regionArea>
<placeName><settlement type="city">Vienne (Autriche)</settlement>
<region nuts="2" type="province">Vienne (Autriche)</region>
</placeName>
</affiliation>
<affiliation wicri:level="3"><nlm:affiliation>Department of Internal Medicine III, Clinical Division of Nephrology and Dialysis, Medical University Vienna, Vienna, Austria.</nlm:affiliation>
<country xml:lang="fr">Autriche</country>
<wicri:regionArea>Department of Internal Medicine III, Clinical Division of Nephrology and Dialysis, Medical University Vienna, Vienna</wicri:regionArea>
<placeName><settlement type="city">Vienne (Autriche)</settlement>
<region nuts="2" type="province">Vienne (Autriche)</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Kernbauer, Elisabeth" sort="Kernbauer, Elisabeth" uniqKey="Kernbauer E" first="Elisabeth" last="Kernbauer">Elisabeth Kernbauer</name>
<affiliation wicri:level="3"><nlm:affiliation>Max F. Perutz Laboratories, Department of Microbiology and Immunobiology, University of Vienna, Vienna, Austria.</nlm:affiliation>
<country xml:lang="fr">Autriche</country>
<wicri:regionArea>Max F. Perutz Laboratories, Department of Microbiology and Immunobiology, University of Vienna, Vienna</wicri:regionArea>
<placeName><settlement type="city">Vienne (Autriche)</settlement>
<region nuts="2" type="province">Vienne (Autriche)</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Holzl, Markus A" sort="Holzl, Markus A" uniqKey="Holzl M" first="Markus A" last="Hölzl">Markus A. Hölzl</name>
<affiliation wicri:level="3"><nlm:affiliation>Institute of Immunology, Center of Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria.</nlm:affiliation>
<country xml:lang="fr">Autriche</country>
<wicri:regionArea>Institute of Immunology, Center of Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna</wicri:regionArea>
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<author><name sortKey="Hofer, Johannes" sort="Hofer, Johannes" uniqKey="Hofer J" first="Johannes" last="Hofer">Johannes Hofer</name>
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<country xml:lang="fr">Autriche</country>
<wicri:regionArea>Institute of Immunology, Center of Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna</wicri:regionArea>
<placeName><settlement type="city">Vienne (Autriche)</settlement>
<region nuts="2" type="province">Vienne (Autriche)</region>
</placeName>
</affiliation>
<affiliation wicri:level="3"><nlm:affiliation>Department of Internal Medicine III, Clinical Division of Nephrology and Dialysis, Medical University Vienna, Vienna, Austria.</nlm:affiliation>
<country xml:lang="fr">Autriche</country>
<wicri:regionArea>Department of Internal Medicine III, Clinical Division of Nephrology and Dialysis, Medical University Vienna, Vienna</wicri:regionArea>
<placeName><settlement type="city">Vienne (Autriche)</settlement>
<region nuts="2" type="province">Vienne (Autriche)</region>
</placeName>
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<author><name sortKey="Gualdoni, Guido A" sort="Gualdoni, Guido A" uniqKey="Gualdoni G" first="Guido A" last="Gualdoni">Guido A. Gualdoni</name>
<affiliation wicri:level="3"><nlm:affiliation>Institute of Immunology, Center of Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria.</nlm:affiliation>
<country xml:lang="fr">Autriche</country>
<wicri:regionArea>Institute of Immunology, Center of Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna</wicri:regionArea>
<placeName><settlement type="city">Vienne (Autriche)</settlement>
<region nuts="2" type="province">Vienne (Autriche)</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Schmetterer, Klaus G" sort="Schmetterer, Klaus G" uniqKey="Schmetterer K" first="Klaus G" last="Schmetterer">Klaus G. Schmetterer</name>
<affiliation wicri:level="3"><nlm:affiliation>Department of Laboratory Medicine, Medical University of Vienna, Vienna, Austria.</nlm:affiliation>
<country xml:lang="fr">Autriche</country>
<wicri:regionArea>Department of Laboratory Medicine, Medical University of Vienna, Vienna</wicri:regionArea>
<placeName><settlement type="city">Vienne (Autriche)</settlement>
<region nuts="2" type="province">Vienne (Autriche)</region>
</placeName>
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<author><name sortKey="Miftari, Fitore" sort="Miftari, Fitore" uniqKey="Miftari F" first="Fitore" last="Miftari">Fitore Miftari</name>
<affiliation wicri:level="3"><nlm:affiliation>Institute of Immunology, Center of Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria.</nlm:affiliation>
<country xml:lang="fr">Autriche</country>
<wicri:regionArea>Institute of Immunology, Center of Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna</wicri:regionArea>
<placeName><settlement type="city">Vienne (Autriche)</settlement>
<region nuts="2" type="province">Vienne (Autriche)</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Sobanov, Yury" sort="Sobanov, Yury" uniqKey="Sobanov Y" first="Yury" last="Sobanov">Yury Sobanov</name>
<affiliation wicri:level="3"><nlm:affiliation>Department of Pathophysiology and Allergy Research, Center of Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria.</nlm:affiliation>
<country xml:lang="fr">Autriche</country>
<wicri:regionArea>Department of Pathophysiology and Allergy Research, Center of Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna</wicri:regionArea>
<placeName><settlement type="city">Vienne (Autriche)</settlement>
<region nuts="2" type="province">Vienne (Autriche)</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Meshcheryakova, Anastasia" sort="Meshcheryakova, Anastasia" uniqKey="Meshcheryakova A" first="Anastasia" last="Meshcheryakova">Anastasia Meshcheryakova</name>
<affiliation wicri:level="3"><nlm:affiliation>Department of Pathophysiology and Allergy Research, Center of Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria.</nlm:affiliation>
<country xml:lang="fr">Autriche</country>
<wicri:regionArea>Department of Pathophysiology and Allergy Research, Center of Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna</wicri:regionArea>
<placeName><settlement type="city">Vienne (Autriche)</settlement>
<region nuts="2" type="province">Vienne (Autriche)</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Mechtcheriakova, Diana" sort="Mechtcheriakova, Diana" uniqKey="Mechtcheriakova D" first="Diana" last="Mechtcheriakova">Diana Mechtcheriakova</name>
<affiliation wicri:level="3"><nlm:affiliation>Department of Pathophysiology and Allergy Research, Center of Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria.</nlm:affiliation>
<country xml:lang="fr">Autriche</country>
<wicri:regionArea>Department of Pathophysiology and Allergy Research, Center of Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna</wicri:regionArea>
<placeName><settlement type="city">Vienne (Autriche)</settlement>
<region nuts="2" type="province">Vienne (Autriche)</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Witzeneder, Nadine" sort="Witzeneder, Nadine" uniqKey="Witzeneder N" first="Nadine" last="Witzeneder">Nadine Witzeneder</name>
<affiliation wicri:level="3"><nlm:affiliation>Department of Laboratory Medicine, Medical University of Vienna, Vienna, Austria.</nlm:affiliation>
<country xml:lang="fr">Autriche</country>
<wicri:regionArea>Department of Laboratory Medicine, Medical University of Vienna, Vienna</wicri:regionArea>
<placeName><settlement type="city">Vienne (Autriche)</settlement>
<region nuts="2" type="province">Vienne (Autriche)</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Greiner, Georg" sort="Greiner, Georg" uniqKey="Greiner G" first="Georg" last="Greiner">Georg Greiner</name>
<affiliation wicri:level="3"><nlm:affiliation>Department of Laboratory Medicine, Medical University of Vienna, Vienna, Austria.</nlm:affiliation>
<country xml:lang="fr">Autriche</country>
<wicri:regionArea>Department of Laboratory Medicine, Medical University of Vienna, Vienna</wicri:regionArea>
<placeName><settlement type="city">Vienne (Autriche)</settlement>
<region nuts="2" type="province">Vienne (Autriche)</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Ohradanova Repic, Anna" sort="Ohradanova Repic, Anna" uniqKey="Ohradanova Repic A" first="Anna" last="Ohradanova-Repic">Anna Ohradanova-Repic</name>
<affiliation wicri:level="3"><nlm:affiliation>Institute of Hygiene and Applied Immunology, Center of Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria.</nlm:affiliation>
<country xml:lang="fr">Autriche</country>
<wicri:regionArea>Institute of Hygiene and Applied Immunology, Center of Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna</wicri:regionArea>
<placeName><settlement type="city">Vienne (Autriche)</settlement>
<region nuts="2" type="province">Vienne (Autriche)</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Waidhofer Sollner, Petra" sort="Waidhofer Sollner, Petra" uniqKey="Waidhofer Sollner P" first="Petra" last="Waidhofer-Söllner">Petra Waidhofer-Söllner</name>
<affiliation wicri:level="3"><nlm:affiliation>Institute of Immunology, Center of Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria.</nlm:affiliation>
<country xml:lang="fr">Autriche</country>
<wicri:regionArea>Institute of Immunology, Center of Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna</wicri:regionArea>
<placeName><settlement type="city">Vienne (Autriche)</settlement>
<region nuts="2" type="province">Vienne (Autriche)</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="S Emann, Marcus D" sort="S Emann, Marcus D" uniqKey="S Emann M" first="Marcus D" last="S Emann">Marcus D. S Emann</name>
<affiliation wicri:level="3"><nlm:affiliation>Department of Internal Medicine III, Clinical Division of Nephrology and Dialysis, Medical University Vienna, Vienna, Austria.</nlm:affiliation>
<country xml:lang="fr">Autriche</country>
<wicri:regionArea>Department of Internal Medicine III, Clinical Division of Nephrology and Dialysis, Medical University Vienna, Vienna</wicri:regionArea>
<placeName><settlement type="city">Vienne (Autriche)</settlement>
<region nuts="2" type="province">Vienne (Autriche)</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Decker, Thomas" sort="Decker, Thomas" uniqKey="Decker T" first="Thomas" last="Decker">Thomas Decker</name>
<affiliation wicri:level="3"><nlm:affiliation>Max F. Perutz Laboratories, Department of Microbiology and Immunobiology, University of Vienna, Vienna, Austria.</nlm:affiliation>
<country xml:lang="fr">Autriche</country>
<wicri:regionArea>Max F. Perutz Laboratories, Department of Microbiology and Immunobiology, University of Vienna, Vienna</wicri:regionArea>
<placeName><settlement type="city">Vienne (Autriche)</settlement>
<region nuts="2" type="province">Vienne (Autriche)</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Zlabinger, Gerhard J" sort="Zlabinger, Gerhard J" uniqKey="Zlabinger G" first="Gerhard J" last="Zlabinger">Gerhard J. Zlabinger</name>
<affiliation wicri:level="3"><nlm:affiliation>Institute of Immunology, Center of Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria.</nlm:affiliation>
<country xml:lang="fr">Autriche</country>
<wicri:regionArea>Institute of Immunology, Center of Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna</wicri:regionArea>
<placeName><settlement type="city">Vienne (Autriche)</settlement>
<region nuts="2" type="province">Vienne (Autriche)</region>
</placeName>
</affiliation>
</author>
</analytic>
<series><title level="j">PloS one</title>
<idno type="eISSN">1932-6203</idno>
<imprint><date when="2017" type="published">2017</date>
</imprint>
</series>
</biblStruct>
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<profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>AMP-Activated Protein Kinases (metabolism)</term>
<term>Animals (MeSH)</term>
<term>Bacterial Load (MeSH)</term>
<term>Cells, Cultured (MeSH)</term>
<term>Deoxyglucose (pharmacology)</term>
<term>Disease Models, Animal (MeSH)</term>
<term>Fasting (metabolism)</term>
<term>Female (MeSH)</term>
<term>Humans (MeSH)</term>
<term>Interleukin-10 (metabolism)</term>
<term>Interleukin-12 (metabolism)</term>
<term>Listeriosis (immunology)</term>
<term>Listeriosis (metabolism)</term>
<term>Listeriosis (microbiology)</term>
<term>Metabolome (MeSH)</term>
<term>Mice (MeSH)</term>
<term>Mice, Inbred BALB C (MeSH)</term>
<term>Myeloid Cells (drug effects)</term>
<term>Myeloid Cells (immunology)</term>
<term>Myeloid Cells (metabolism)</term>
<term>Signal Transduction (MeSH)</term>
<term>TOR Serine-Threonine Kinases (metabolism)</term>
<term>Toll-Like Receptors (metabolism)</term>
</keywords>
<keywords scheme="KwdFr" xml:lang="fr"><term>AMP-Activated Protein Kinases (métabolisme)</term>
<term>Animaux (MeSH)</term>
<term>Cellules cultivées (MeSH)</term>
<term>Cellules myéloïdes (effets des médicaments et des substances chimiques)</term>
<term>Cellules myéloïdes (immunologie)</term>
<term>Cellules myéloïdes (métabolisme)</term>
<term>Charge bactérienne (MeSH)</term>
<term>Désoxyglucose (pharmacologie)</term>
<term>Femelle (MeSH)</term>
<term>Humains (MeSH)</term>
<term>Infections à Listeria (immunologie)</term>
<term>Infections à Listeria (microbiologie)</term>
<term>Infections à Listeria (métabolisme)</term>
<term>Interleukine-10 (métabolisme)</term>
<term>Interleukine-12 (métabolisme)</term>
<term>Jeûne (métabolisme)</term>
<term>Modèles animaux de maladie humaine (MeSH)</term>
<term>Métabolome (MeSH)</term>
<term>Récepteurs de type Toll (métabolisme)</term>
<term>Souris (MeSH)</term>
<term>Souris de lignée BALB C (MeSH)</term>
<term>Sérine-thréonine kinases TOR (métabolisme)</term>
<term>Transduction du signal (MeSH)</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>AMP-Activated Protein Kinases</term>
<term>Interleukin-10</term>
<term>Interleukin-12</term>
<term>TOR Serine-Threonine Kinases</term>
<term>Toll-Like Receptors</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="pharmacology" xml:lang="en"><term>Deoxyglucose</term>
</keywords>
<keywords scheme="MESH" qualifier="drug effects" xml:lang="en"><term>Myeloid Cells</term>
</keywords>
<keywords scheme="MESH" qualifier="effets des médicaments et des substances chimiques" xml:lang="fr"><term>Cellules myéloïdes</term>
</keywords>
<keywords scheme="MESH" qualifier="immunologie" xml:lang="fr"><term>Cellules myéloïdes</term>
<term>Infections à Listeria</term>
</keywords>
<keywords scheme="MESH" qualifier="immunology" xml:lang="en"><term>Listeriosis</term>
<term>Myeloid Cells</term>
</keywords>
<keywords scheme="MESH" qualifier="metabolism" xml:lang="en"><term>Fasting</term>
<term>Listeriosis</term>
<term>Myeloid Cells</term>
</keywords>
<keywords scheme="MESH" qualifier="microbiologie" xml:lang="fr"><term>Infections à Listeria</term>
</keywords>
<keywords scheme="MESH" qualifier="microbiology" xml:lang="en"><term>Listeriosis</term>
</keywords>
<keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr"><term>AMP-Activated Protein Kinases</term>
<term>Cellules myéloïdes</term>
<term>Infections à Listeria</term>
<term>Interleukine-10</term>
<term>Interleukine-12</term>
<term>Jeûne</term>
<term>Récepteurs de type Toll</term>
<term>Sérine-thréonine kinases TOR</term>
</keywords>
<keywords scheme="MESH" qualifier="pharmacologie" xml:lang="fr"><term>Désoxyglucose</term>
</keywords>
<keywords scheme="MESH" xml:lang="en"><term>Animals</term>
<term>Bacterial Load</term>
<term>Cells, Cultured</term>
<term>Disease Models, Animal</term>
<term>Female</term>
<term>Humans</term>
<term>Metabolome</term>
<term>Mice</term>
<term>Mice, Inbred BALB C</term>
<term>Signal Transduction</term>
</keywords>
<keywords scheme="MESH" xml:lang="fr"><term>Animaux</term>
<term>Cellules cultivées</term>
<term>Charge bactérienne</term>
<term>Femelle</term>
<term>Humains</term>
<term>Modèles animaux de maladie humaine</term>
<term>Métabolome</term>
<term>Souris</term>
<term>Souris de lignée BALB C</term>
<term>Transduction du signal</term>
</keywords>
</textClass>
</profileDesc>
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<front><div type="abstract" xml:lang="en">A crucial role of cell metabolism in immune cell differentiation and function has been recently established. Growing evidence indicates that metabolic processes impact both, innate and adaptive immunity. Since a down-stream integrator of metabolic alterations, mammalian target of rapamycin (mTOR), is responsible for controlling the balance between pro-inflammatory interleukin (IL)-12 and anti-inflammatory IL-10, we investigated the effect of upstream interference using metabolic modulators on the production of pro- and anti-inflammatory cytokines. Cytokine release and protein expression in human and murine myeloid cells was assessed after toll-like receptor (TLR)-activation and glucose-deprivation or co-treatment with 5'-adenosine monophosphate (AMP)-activated protein kinase (AMPK) activators. Additionally, the impact of metabolic interference was analysed in an in-vivo mouse model. Glucose-deprivation by 2-deoxy-D-glucose (2-DG) increased the production of IL-12p40 and IL-23p19 in monocytes, but dose-dependently inhibited the release of anti-inflammatory IL-10. Similar effects have been observed using pharmacological AMPK activation. Consistently, an inhibition of the tuberous sclerosis complex-mTOR pathway was observed. In line with our in vitro observations, glycolysis inhibition with 2-DG showed significantly reduced bacterial burden in a Th2-prone Listeria monocytogenes mouse infection model. In conclusion, we showed that fasting metabolism modulates the IL-12/IL-10 cytokine balance, establishing novel targets for metabolism-based immune-modulation.</div>
</front>
</TEI>
<pubmed><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">28742108</PMID>
<DateCompleted><Year>2017</Year>
<Month>09</Month>
<Day>25</Day>
</DateCompleted>
<DateRevised><Year>2018</Year>
<Month>11</Month>
<Day>13</Day>
</DateRevised>
<Article PubModel="Electronic-eCollection"><Journal><ISSN IssnType="Electronic">1932-6203</ISSN>
<JournalIssue CitedMedium="Internet"><Volume>12</Volume>
<Issue>7</Issue>
<PubDate><Year>2017</Year>
</PubDate>
</JournalIssue>
<Title>PloS one</Title>
<ISOAbbreviation>PLoS One</ISOAbbreviation>
</Journal>
<ArticleTitle>Fasting metabolism modulates the interleukin-12/interleukin-10 cytokine axis.</ArticleTitle>
<Pagination><MedlinePgn>e0180900</MedlinePgn>
</Pagination>
<ELocationID EIdType="doi" ValidYN="Y">10.1371/journal.pone.0180900</ELocationID>
<Abstract><AbstractText>A crucial role of cell metabolism in immune cell differentiation and function has been recently established. Growing evidence indicates that metabolic processes impact both, innate and adaptive immunity. Since a down-stream integrator of metabolic alterations, mammalian target of rapamycin (mTOR), is responsible for controlling the balance between pro-inflammatory interleukin (IL)-12 and anti-inflammatory IL-10, we investigated the effect of upstream interference using metabolic modulators on the production of pro- and anti-inflammatory cytokines. Cytokine release and protein expression in human and murine myeloid cells was assessed after toll-like receptor (TLR)-activation and glucose-deprivation or co-treatment with 5'-adenosine monophosphate (AMP)-activated protein kinase (AMPK) activators. Additionally, the impact of metabolic interference was analysed in an in-vivo mouse model. Glucose-deprivation by 2-deoxy-D-glucose (2-DG) increased the production of IL-12p40 and IL-23p19 in monocytes, but dose-dependently inhibited the release of anti-inflammatory IL-10. Similar effects have been observed using pharmacological AMPK activation. Consistently, an inhibition of the tuberous sclerosis complex-mTOR pathway was observed. In line with our in vitro observations, glycolysis inhibition with 2-DG showed significantly reduced bacterial burden in a Th2-prone Listeria monocytogenes mouse infection model. In conclusion, we showed that fasting metabolism modulates the IL-12/IL-10 cytokine balance, establishing novel targets for metabolism-based immune-modulation.</AbstractText>
</Abstract>
<AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Kovarik</LastName>
<ForeName>Johannes J</ForeName>
<Initials>JJ</Initials>
<Identifier Source="ORCID">http://orcid.org/0000-0002-0206-082X</Identifier>
<AffiliationInfo><Affiliation>Institute of Immunology, Center of Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>Department of Internal Medicine III, Clinical Division of Nephrology and Dialysis, Medical University Vienna, Vienna, Austria.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Kernbauer</LastName>
<ForeName>Elisabeth</ForeName>
<Initials>E</Initials>
<AffiliationInfo><Affiliation>Max F. Perutz Laboratories, Department of Microbiology and Immunobiology, University of Vienna, Vienna, Austria.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Hölzl</LastName>
<ForeName>Markus A</ForeName>
<Initials>MA</Initials>
<AffiliationInfo><Affiliation>Institute of Immunology, Center of Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Hofer</LastName>
<ForeName>Johannes</ForeName>
<Initials>J</Initials>
<AffiliationInfo><Affiliation>Institute of Immunology, Center of Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>Department of Internal Medicine III, Clinical Division of Nephrology and Dialysis, Medical University Vienna, Vienna, Austria.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Gualdoni</LastName>
<ForeName>Guido A</ForeName>
<Initials>GA</Initials>
<AffiliationInfo><Affiliation>Institute of Immunology, Center of Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Schmetterer</LastName>
<ForeName>Klaus G</ForeName>
<Initials>KG</Initials>
<AffiliationInfo><Affiliation>Department of Laboratory Medicine, Medical University of Vienna, Vienna, Austria.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Miftari</LastName>
<ForeName>Fitore</ForeName>
<Initials>F</Initials>
<AffiliationInfo><Affiliation>Institute of Immunology, Center of Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Sobanov</LastName>
<ForeName>Yury</ForeName>
<Initials>Y</Initials>
<AffiliationInfo><Affiliation>Department of Pathophysiology and Allergy Research, Center of Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Meshcheryakova</LastName>
<ForeName>Anastasia</ForeName>
<Initials>A</Initials>
<AffiliationInfo><Affiliation>Department of Pathophysiology and Allergy Research, Center of Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Mechtcheriakova</LastName>
<ForeName>Diana</ForeName>
<Initials>D</Initials>
<AffiliationInfo><Affiliation>Department of Pathophysiology and Allergy Research, Center of Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Witzeneder</LastName>
<ForeName>Nadine</ForeName>
<Initials>N</Initials>
<AffiliationInfo><Affiliation>Department of Laboratory Medicine, Medical University of Vienna, Vienna, Austria.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Greiner</LastName>
<ForeName>Georg</ForeName>
<Initials>G</Initials>
<AffiliationInfo><Affiliation>Department of Laboratory Medicine, Medical University of Vienna, Vienna, Austria.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Ohradanova-Repic</LastName>
<ForeName>Anna</ForeName>
<Initials>A</Initials>
<AffiliationInfo><Affiliation>Institute of Hygiene and Applied Immunology, Center of Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Waidhofer-Söllner</LastName>
<ForeName>Petra</ForeName>
<Initials>P</Initials>
<AffiliationInfo><Affiliation>Institute of Immunology, Center of Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Säemann</LastName>
<ForeName>Marcus D</ForeName>
<Initials>MD</Initials>
<AffiliationInfo><Affiliation>Department of Internal Medicine III, Clinical Division of Nephrology and Dialysis, Medical University Vienna, Vienna, Austria.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Decker</LastName>
<ForeName>Thomas</ForeName>
<Initials>T</Initials>
<AffiliationInfo><Affiliation>Max F. Perutz Laboratories, Department of Microbiology and Immunobiology, University of Vienna, Vienna, Austria.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Zlabinger</LastName>
<ForeName>Gerhard J</ForeName>
<Initials>GJ</Initials>
<Identifier Source="ORCID">http://orcid.org/0000-0002-7478-4173</Identifier>
<AffiliationInfo><Affiliation>Institute of Immunology, Center of Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria.</Affiliation>
</AffiliationInfo>
</Author>
</AuthorList>
<Language>eng</Language>
<GrantList CompleteYN="Y"><Grant><GrantID>P 22441</GrantID>
<Agency>Austrian Science Fund FWF</Agency>
<Country>Austria</Country>
</Grant>
<Grant><GrantID>P 23228</GrantID>
<Agency>Austrian Science Fund FWF</Agency>
<Country>Austria</Country>
</Grant>
</GrantList>
<PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType>
</PublicationTypeList>
<ArticleDate DateType="Electronic"><Year>2017</Year>
<Month>07</Month>
<Day>24</Day>
</ArticleDate>
</Article>
<MedlineJournalInfo><Country>United States</Country>
<MedlineTA>PLoS One</MedlineTA>
<NlmUniqueID>101285081</NlmUniqueID>
<ISSNLinking>1932-6203</ISSNLinking>
</MedlineJournalInfo>
<ChemicalList><Chemical><RegistryNumber>0</RegistryNumber>
<NameOfSubstance UI="D051193">Toll-Like Receptors</NameOfSubstance>
</Chemical>
<Chemical><RegistryNumber>130068-27-8</RegistryNumber>
<NameOfSubstance UI="D016753">Interleukin-10</NameOfSubstance>
</Chemical>
<Chemical><RegistryNumber>187348-17-0</RegistryNumber>
<NameOfSubstance UI="D018664">Interleukin-12</NameOfSubstance>
</Chemical>
<Chemical><RegistryNumber>9G2MP84A8W</RegistryNumber>
<NameOfSubstance UI="D003847">Deoxyglucose</NameOfSubstance>
</Chemical>
<Chemical><RegistryNumber>EC 2.7.1.1</RegistryNumber>
<NameOfSubstance UI="D058570">TOR Serine-Threonine Kinases</NameOfSubstance>
</Chemical>
<Chemical><RegistryNumber>EC 2.7.11.31</RegistryNumber>
<NameOfSubstance UI="D055372">AMP-Activated Protein Kinases</NameOfSubstance>
</Chemical>
</ChemicalList>
<CitationSubset>IM</CitationSubset>
<MeshHeadingList><MeshHeading><DescriptorName UI="D055372" MajorTopicYN="N">AMP-Activated Protein Kinases</DescriptorName>
<QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D000818" MajorTopicYN="N">Animals</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D058491" MajorTopicYN="N">Bacterial Load</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D002478" MajorTopicYN="N">Cells, Cultured</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D003847" MajorTopicYN="N">Deoxyglucose</DescriptorName>
<QualifierName UI="Q000494" MajorTopicYN="N">pharmacology</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D004195" MajorTopicYN="N">Disease Models, Animal</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D005215" MajorTopicYN="N">Fasting</DescriptorName>
<QualifierName UI="Q000378" MajorTopicYN="Y">metabolism</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D005260" MajorTopicYN="N">Female</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D006801" MajorTopicYN="N">Humans</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D016753" MajorTopicYN="N">Interleukin-10</DescriptorName>
<QualifierName UI="Q000378" MajorTopicYN="Y">metabolism</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D018664" MajorTopicYN="N">Interleukin-12</DescriptorName>
<QualifierName UI="Q000378" MajorTopicYN="Y">metabolism</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D008088" MajorTopicYN="N">Listeriosis</DescriptorName>
<QualifierName UI="Q000276" MajorTopicYN="N">immunology</QualifierName>
<QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName>
<QualifierName UI="Q000382" MajorTopicYN="N">microbiology</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D055442" MajorTopicYN="N">Metabolome</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D051379" MajorTopicYN="N">Mice</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D008807" MajorTopicYN="N">Mice, Inbred BALB C</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D022423" MajorTopicYN="N">Myeloid Cells</DescriptorName>
<QualifierName UI="Q000187" MajorTopicYN="N">drug effects</QualifierName>
<QualifierName UI="Q000276" MajorTopicYN="N">immunology</QualifierName>
<QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D015398" MajorTopicYN="N">Signal Transduction</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D058570" MajorTopicYN="N">TOR Serine-Threonine Kinases</DescriptorName>
<QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName>
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	Serveur d'exploration sur la rapamycine et les champignons
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Fasting metabolism modulates the interleukin-12/interleukin-10 cytokine axis.

Fasting metabolism modulates the interleukin-12/interleukin-10 cytokine axis.

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