RapamycinFungusV1, Main, Exploration, bibRecord, 000284

Metformin Alters Human Host Responses to Mycobacterium tuberculosis in Healthy Subjects.

Identifieur interne : 000284 ( Main/Exploration ); précédent : 000283; suivant : 000285

Metformin Alters Human Host Responses to Mycobacterium tuberculosis in Healthy Subjects.

Auteurs : Ekta Lachmandas [Pays-Bas] ; Clare Eckold [Royaume-Uni] ; Julia Böhme ; Valerie A C M. Koeken [Pays-Bas] ; Mardiana Binte Marzuki ; Bastiaan Blok [Pays-Bas] ; Rob J W. Arts [Pays-Bas] ; Jinmiao Chen ; Karen W W. Teng ; Jacqueline Ratter [Pays-Bas] ; Elise J. Smolders [Pays-Bas] ; Corina Van Den Heuvel [Pays-Bas] ; Rinke Stienstra [Pays-Bas] ; Hazel M. Dockrell [Royaume-Uni] ; Evan Newell ; Mihai G. Netea [Pays-Bas, Roumanie] ; Amit Singhal [Singapour] ; Jacqueline M. Cliff [Royaume-Uni] ; Reinout Van Crevel [Pays-Bas]

Source :

The Journal of infectious diseases [ 1537-6613 ] ; 2019.

RBID : pubmed:30753544

Descripteurs français

KwdFr :
- Agranulocytes (effets des médicaments et des substances chimiques), Agranulocytes (microbiologie), Cellules myéloïdes (effets des médicaments et des substances chimiques), Cellules myéloïdes (métabolisme), Espèces réactives de l'oxygène (métabolisme), Humains (MeSH), Hypoglycémiants (pharmacologie), Interactions hôte-pathogène (effets des médicaments et des substances chimiques), Metformine (pharmacologie), Monocytes (effets des médicaments et des substances chimiques), Monocytes (métabolisme), Mycobacterium tuberculosis (pathogénicité), Phagocytose (effets des médicaments et des substances chimiques), Prolifération cellulaire (effets des médicaments et des substances chimiques), Régulation négative (effets des médicaments et des substances chimiques), Régulation positive (effets des médicaments et des substances chimiques), Transduction du signal (effets des médicaments et des substances chimiques), Tuberculose (microbiologie), Tuberculose (métabolisme), Volontaires sains (MeSH).
MESH :
- effets des médicaments et des substances chimiques : Agranulocytes, Cellules myéloïdes, Interactions hôte-pathogène, Monocytes, Phagocytose, Prolifération cellulaire, Régulation négative, Régulation positive, Transduction du signal.
- microbiologie : Agranulocytes, Tuberculose.
- métabolisme : Cellules myéloïdes, Espèces réactives de l'oxygène, Monocytes, Tuberculose.
- pathogénicité : Mycobacterium tuberculosis.
- pharmacologie : Hypoglycémiants, Metformine.
- Humains, Volontaires sains.

English descriptors

KwdEn :
- Cell Proliferation (drug effects), Down-Regulation (drug effects), Healthy Volunteers (MeSH), Host-Pathogen Interactions (drug effects), Humans (MeSH), Hypoglycemic Agents (pharmacology), Leukocytes, Mononuclear (drug effects), Leukocytes, Mononuclear (microbiology), Metformin (pharmacology), Monocytes (drug effects), Monocytes (metabolism), Mycobacterium tuberculosis (pathogenicity), Myeloid Cells (drug effects), Myeloid Cells (metabolism), Phagocytosis (drug effects), Reactive Oxygen Species (metabolism), Signal Transduction (drug effects), Tuberculosis (metabolism), Tuberculosis (microbiology), Up-Regulation (drug effects).
MESH :
- chemical , metabolism : Reactive Oxygen Species.
- chemical , pharmacology : Hypoglycemic Agents, Metformin.
- drug effects : Cell Proliferation, Down-Regulation, Host-Pathogen Interactions, Leukocytes, Mononuclear, Monocytes, Myeloid Cells, Phagocytosis, Signal Transduction, Up-Regulation.
- metabolism : Monocytes, Myeloid Cells, Tuberculosis.
- microbiology : Leukocytes, Mononuclear, Tuberculosis.
- pathogenicity : Mycobacterium tuberculosis.
- Healthy Volunteers, Humans.

Abstract

BACKGROUND

Metformin, the most widely administered diabetes drug, has been proposed as a candidate adjunctive host-directed therapy for tuberculosis, but little is known about its effects on human host responses to Mycobacterium tuberculosis.

METHODS

We investigated in vitro and in vivo effects of metformin in humans.

RESULTS

Metformin added to peripheral blood mononuclear cells from healthy volunteers enhanced in vitro cellular metabolism while inhibiting the mammalian target of rapamycin targets p70S6K and 4EBP1, with decreased cytokine production and cellular proliferation and increased phagocytosis activity. Metformin administered to healthy human volunteers led to significant downregulation of genes involved in oxidative phosphorylation, mammalian target of rapamycin signaling, and type I interferon response pathways, particularly following stimulation with M. tuberculosis, and upregulation of genes involved in phagocytosis and reactive oxygen species production was increased. These in vivo effects were accompanied by a metformin-induced shift in myeloid cells from classical to nonclassical monocytes. At a functional level, metformin lowered ex vivo production of tumor necrosis factor α, interferon γ, and interleukin 1β but increased phagocytosis activity and reactive oxygen species production.

CONCLUSION

Metformin has a range of potentially beneficial effects on cellular metabolism, immune function, and gene transcription involved in innate host responses to M. tuberculosis.

DOI: 10.1093/infdis/jiz064
PubMed: 30753544
PubMed Central: PMC6548897

Affiliations:

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

to stream Main, to step Corpus: 000342
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Le document en format XML

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<author><name sortKey="Smolders, Elise J" sort="Smolders, Elise J" uniqKey="Smolders E" first="Elise J" last="Smolders">Elise J. Smolders</name>
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<author><name sortKey="Van Den Heuvel, Corina" sort="Van Den Heuvel, Corina" uniqKey="Van Den Heuvel C" first="Corina" last="Van Den Heuvel">Corina Van Den Heuvel</name>
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<author><name sortKey="Stienstra, Rinke" sort="Stienstra, Rinke" uniqKey="Stienstra R" first="Rinke" last="Stienstra">Rinke Stienstra</name>
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<author><name sortKey="Dockrell, Hazel M" sort="Dockrell, Hazel M" uniqKey="Dockrell H" first="Hazel M" last="Dockrell">Hazel M. Dockrell</name>
<affiliation wicri:level="1"><nlm:affiliation>Department of Immunology and Infection, Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, United Kingdom.</nlm:affiliation>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>Department of Immunology and Infection, Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine</wicri:regionArea>
<wicri:noRegion>London School of Hygiene and Tropical Medicine</wicri:noRegion>
</affiliation>
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<author><name sortKey="Newell, Evan" sort="Newell, Evan" uniqKey="Newell E" first="Evan" last="Newell">Evan Newell</name>
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</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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<country>Pays-Bas</country>
<placeName><settlement type="city">Nimègue</settlement>
<region type="province" nuts="2">Gueldre</region>
</placeName>
<wicri:orgArea>Department of Internal Medicine</wicri:orgArea>
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<country>Pays-Bas</country>
<placeName><settlement type="city">Nimègue</settlement>
<region type="province" nuts="2">Gueldre</region>
</placeName>
<wicri:orgArea>Radboud Center for Infectious Diseases, Radboud University Medical Center</wicri:orgArea>
</affiliation>
<affiliation wicri:level="1"><nlm:affiliation>Human Genomics Laboratory, Craiova University of Medicine and Pharmacy, Romania.</nlm:affiliation>
<country xml:lang="fr">Roumanie</country>
<wicri:regionArea>Human Genomics Laboratory, Craiova University of Medicine and Pharmacy</wicri:regionArea>
<wicri:noRegion>Craiova University of Medicine and Pharmacy</wicri:noRegion>
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<author><name sortKey="Singhal, Amit" sort="Singhal, Amit" uniqKey="Singhal A" first="Amit" last="Singhal">Amit Singhal</name>
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<wicri:noCountry code="subField">and Research</wicri:noCountry>
</affiliation>
<affiliation wicri:level="1"><nlm:affiliation>Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore.</nlm:affiliation>
<country xml:lang="fr">Singapour</country>
<wicri:regionArea>Lee Kong Chian School of Medicine, Nanyang Technological University</wicri:regionArea>
<wicri:noRegion>Nanyang Technological University</wicri:noRegion>
</affiliation>
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<author><name sortKey="Cliff, Jacqueline M" sort="Cliff, Jacqueline M" uniqKey="Cliff J" first="Jacqueline M" last="Cliff">Jacqueline M. Cliff</name>
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<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>Department of Immunology and Infection, Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine</wicri:regionArea>
<wicri:noRegion>London School of Hygiene and Tropical Medicine</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Van Crevel, Reinout" sort="Van Crevel, Reinout" uniqKey="Van Crevel R" first="Reinout" last="Van Crevel">Reinout Van Crevel</name>
<affiliation wicri:level="3"><nlm:affiliation>Department of Internal Medicine, Nijmegen.</nlm:affiliation>
<country>Pays-Bas</country>
<placeName><settlement type="city">Nimègue</settlement>
<region type="province" nuts="2">Gueldre</region>
</placeName>
<wicri:orgArea>Department of Internal Medicine</wicri:orgArea>
</affiliation>
<affiliation wicri:level="3"><nlm:affiliation>Radboud Center for Infectious Diseases, Radboud University Medical Center, Nijmegen.</nlm:affiliation>
<country>Pays-Bas</country>
<placeName><settlement type="city">Nimègue</settlement>
<region type="province" nuts="2">Gueldre</region>
</placeName>
<wicri:orgArea>Radboud Center for Infectious Diseases, Radboud University Medical Center</wicri:orgArea>
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<sourceDesc><biblStruct><analytic><title xml:lang="en">Metformin Alters Human Host Responses to Mycobacterium tuberculosis in Healthy Subjects.</title>
<author><name sortKey="Lachmandas, Ekta" sort="Lachmandas, Ekta" uniqKey="Lachmandas E" first="Ekta" last="Lachmandas">Ekta Lachmandas</name>
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<placeName><settlement type="city">Nimègue</settlement>
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</affiliation>
<affiliation wicri:level="3"><nlm:affiliation>Radboud Center for Infectious Diseases, Radboud University Medical Center, Nijmegen.</nlm:affiliation>
<country>Pays-Bas</country>
<placeName><settlement type="city">Nimègue</settlement>
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</placeName>
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<author><name sortKey="Eckold, Clare" sort="Eckold, Clare" uniqKey="Eckold C" first="Clare" last="Eckold">Clare Eckold</name>
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<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>Department of Immunology and Infection, Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine</wicri:regionArea>
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</affiliation>
</author>
<author><name sortKey="Bohme, Julia" sort="Bohme, Julia" uniqKey="Bohme J" first="Julia" last="Böhme">Julia Böhme</name>
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<wicri:noCountry code="subField">and Research</wicri:noCountry>
</affiliation>
</author>
<author><name sortKey="Koeken, Valerie A C M" sort="Koeken, Valerie A C M" uniqKey="Koeken V" first="Valerie A C M" last="Koeken">Valerie A C M. Koeken</name>
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<placeName><settlement type="city">Nimègue</settlement>
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</placeName>
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</affiliation>
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</affiliation>
</author>
<author><name sortKey="Marzuki, Mardiana Binte" sort="Marzuki, Mardiana Binte" uniqKey="Marzuki M" first="Mardiana Binte" last="Marzuki">Mardiana Binte Marzuki</name>
<affiliation><nlm:affiliation>Singapore Immunology Network, Agency for Science, Technology, and Research.</nlm:affiliation>
<wicri:noCountry code="subField">and Research</wicri:noCountry>
</affiliation>
</author>
<author><name sortKey="Blok, Bastiaan" sort="Blok, Bastiaan" uniqKey="Blok B" first="Bastiaan" last="Blok">Bastiaan Blok</name>
<affiliation wicri:level="3"><nlm:affiliation>Department of Internal Medicine, Nijmegen.</nlm:affiliation>
<country>Pays-Bas</country>
<placeName><settlement type="city">Nimègue</settlement>
<region type="province" nuts="2">Gueldre</region>
</placeName>
<wicri:orgArea>Department of Internal Medicine</wicri:orgArea>
</affiliation>
<affiliation wicri:level="3"><nlm:affiliation>Radboud Center for Infectious Diseases, Radboud University Medical Center, Nijmegen.</nlm:affiliation>
<country>Pays-Bas</country>
<placeName><settlement type="city">Nimègue</settlement>
<region type="province" nuts="2">Gueldre</region>
</placeName>
<wicri:orgArea>Radboud Center for Infectious Diseases, Radboud University Medical Center</wicri:orgArea>
</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="3"><nlm:affiliation>Department of Internal Medicine, Nijmegen.</nlm:affiliation>
<country>Pays-Bas</country>
<placeName><settlement type="city">Nimègue</settlement>
<region type="province" nuts="2">Gueldre</region>
</placeName>
<wicri:orgArea>Department of Internal Medicine</wicri:orgArea>
</affiliation>
<affiliation wicri:level="3"><nlm:affiliation>Radboud Center for Infectious Diseases, Radboud University Medical Center, Nijmegen.</nlm:affiliation>
<country>Pays-Bas</country>
<placeName><settlement type="city">Nimègue</settlement>
<region type="province" nuts="2">Gueldre</region>
</placeName>
<wicri:orgArea>Radboud Center for Infectious Diseases, Radboud University Medical Center</wicri:orgArea>
</affiliation>
</author>
<author><name sortKey="Chen, Jinmiao" sort="Chen, Jinmiao" uniqKey="Chen J" first="Jinmiao" last="Chen">Jinmiao Chen</name>
<affiliation><nlm:affiliation>Singapore Immunology Network, Agency for Science, Technology, and Research.</nlm:affiliation>
<wicri:noCountry code="subField">and Research</wicri:noCountry>
</affiliation>
</author>
<author><name sortKey="Teng, Karen W W" sort="Teng, Karen W W" uniqKey="Teng K" first="Karen W W" last="Teng">Karen W W. Teng</name>
<affiliation><nlm:affiliation>Singapore Immunology Network, Agency for Science, Technology, and Research.</nlm:affiliation>
<wicri:noCountry code="subField">and Research</wicri:noCountry>
</affiliation>
</author>
<author><name sortKey="Ratter, Jacqueline" sort="Ratter, Jacqueline" uniqKey="Ratter J" first="Jacqueline" last="Ratter">Jacqueline Ratter</name>
<affiliation wicri:level="3"><nlm:affiliation>Department of Internal Medicine, Nijmegen.</nlm:affiliation>
<country>Pays-Bas</country>
<placeName><settlement type="city">Nimègue</settlement>
<region type="province" nuts="2">Gueldre</region>
</placeName>
<wicri:orgArea>Department of Internal Medicine</wicri:orgArea>
</affiliation>
<affiliation wicri:level="3"><nlm:affiliation>Radboud Center for Infectious Diseases, Radboud University Medical Center, Nijmegen.</nlm:affiliation>
<country>Pays-Bas</country>
<placeName><settlement type="city">Nimègue</settlement>
<region type="province" nuts="2">Gueldre</region>
</placeName>
<wicri:orgArea>Radboud Center for Infectious Diseases, Radboud University Medical Center</wicri:orgArea>
</affiliation>
<affiliation wicri:level="4"><nlm:affiliation>Nutrition, Metabolism and Genomics Group, Division of Human Nutrition, Wageningen University, Wageningen, the Netherlands.</nlm:affiliation>
<country xml:lang="fr" wicri:curation="lc">Pays-Bas</country>
<wicri:regionArea>Nutrition, Metabolism and Genomics Group, Division of Human Nutrition, Wageningen University, Wageningen</wicri:regionArea>
<orgName type="university">Université de Wageningue</orgName>
<placeName><settlement type="city">Wageningue</settlement>
<region nuts="2">Gueldre (province)</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Smolders, Elise J" sort="Smolders, Elise J" uniqKey="Smolders E" first="Elise J" last="Smolders">Elise J. Smolders</name>
<affiliation wicri:level="3"><nlm:affiliation>Department of Internal Medicine, Nijmegen.</nlm:affiliation>
<country>Pays-Bas</country>
<placeName><settlement type="city">Nimègue</settlement>
<region type="province" nuts="2">Gueldre</region>
</placeName>
<wicri:orgArea>Department of Internal Medicine</wicri:orgArea>
</affiliation>
<affiliation wicri:level="3"><nlm:affiliation>Radboud Center for Infectious Diseases, Radboud University Medical Center, Nijmegen.</nlm:affiliation>
<country>Pays-Bas</country>
<placeName><settlement type="city">Nimègue</settlement>
<region type="province" nuts="2">Gueldre</region>
</placeName>
<wicri:orgArea>Radboud Center for Infectious Diseases, Radboud University Medical Center</wicri:orgArea>
</affiliation>
</author>
<author><name sortKey="Van Den Heuvel, Corina" sort="Van Den Heuvel, Corina" uniqKey="Van Den Heuvel C" first="Corina" last="Van Den Heuvel">Corina Van Den Heuvel</name>
<affiliation wicri:level="3"><nlm:affiliation>Department of Internal Medicine, Nijmegen.</nlm:affiliation>
<country>Pays-Bas</country>
<placeName><settlement type="city">Nimègue</settlement>
<region type="province" nuts="2">Gueldre</region>
</placeName>
<wicri:orgArea>Department of Internal Medicine</wicri:orgArea>
</affiliation>
<affiliation wicri:level="3"><nlm:affiliation>Radboud Center for Infectious Diseases, Radboud University Medical Center, Nijmegen.</nlm:affiliation>
<country>Pays-Bas</country>
<placeName><settlement type="city">Nimègue</settlement>
<region type="province" nuts="2">Gueldre</region>
</placeName>
<wicri:orgArea>Radboud Center for Infectious Diseases, Radboud University Medical Center</wicri:orgArea>
</affiliation>
</author>
<author><name sortKey="Stienstra, Rinke" sort="Stienstra, Rinke" uniqKey="Stienstra R" first="Rinke" last="Stienstra">Rinke Stienstra</name>
<affiliation wicri:level="3"><nlm:affiliation>Department of Internal Medicine, Nijmegen.</nlm:affiliation>
<country>Pays-Bas</country>
<placeName><settlement type="city">Nimègue</settlement>
<region type="province" nuts="2">Gueldre</region>
</placeName>
<wicri:orgArea>Department of Internal Medicine</wicri:orgArea>
</affiliation>
<affiliation wicri:level="3"><nlm:affiliation>Radboud Center for Infectious Diseases, Radboud University Medical Center, Nijmegen.</nlm:affiliation>
<country>Pays-Bas</country>
<placeName><settlement type="city">Nimègue</settlement>
<region type="province" nuts="2">Gueldre</region>
</placeName>
<wicri:orgArea>Radboud Center for Infectious Diseases, Radboud University Medical Center</wicri:orgArea>
</affiliation>
<affiliation wicri:level="4"><nlm:affiliation>Nutrition, Metabolism and Genomics Group, Division of Human Nutrition, Wageningen University, Wageningen, the Netherlands.</nlm:affiliation>
<country xml:lang="fr" wicri:curation="lc">Pays-Bas</country>
<wicri:regionArea>Nutrition, Metabolism and Genomics Group, Division of Human Nutrition, Wageningen University, Wageningen</wicri:regionArea>
<orgName type="university">Université de Wageningue</orgName>
<placeName><settlement type="city">Wageningue</settlement>
<region nuts="2">Gueldre (province)</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Dockrell, Hazel M" sort="Dockrell, Hazel M" uniqKey="Dockrell H" first="Hazel M" last="Dockrell">Hazel M. Dockrell</name>
<affiliation wicri:level="1"><nlm:affiliation>Department of Immunology and Infection, Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, United Kingdom.</nlm:affiliation>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>Department of Immunology and Infection, Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine</wicri:regionArea>
<wicri:noRegion>London School of Hygiene and Tropical Medicine</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Newell, Evan" sort="Newell, Evan" uniqKey="Newell E" first="Evan" last="Newell">Evan Newell</name>
<affiliation><nlm:affiliation>Singapore Immunology Network, Agency for Science, Technology, and Research.</nlm:affiliation>
<wicri:noCountry code="subField">and Research</wicri:noCountry>
</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="3"><nlm:affiliation>Department of Internal Medicine, Nijmegen.</nlm:affiliation>
<country>Pays-Bas</country>
<placeName><settlement type="city">Nimègue</settlement>
<region type="province" nuts="2">Gueldre</region>
</placeName>
<wicri:orgArea>Department of Internal Medicine</wicri:orgArea>
</affiliation>
<affiliation wicri:level="3"><nlm:affiliation>Radboud Center for Infectious Diseases, Radboud University Medical Center, Nijmegen.</nlm:affiliation>
<country>Pays-Bas</country>
<placeName><settlement type="city">Nimègue</settlement>
<region type="province" nuts="2">Gueldre</region>
</placeName>
<wicri:orgArea>Radboud Center for Infectious Diseases, Radboud University Medical Center</wicri:orgArea>
</affiliation>
<affiliation wicri:level="1"><nlm:affiliation>Human Genomics Laboratory, Craiova University of Medicine and Pharmacy, Romania.</nlm:affiliation>
<country xml:lang="fr">Roumanie</country>
<wicri:regionArea>Human Genomics Laboratory, Craiova University of Medicine and Pharmacy</wicri:regionArea>
<wicri:noRegion>Craiova University of Medicine and Pharmacy</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Singhal, Amit" sort="Singhal, Amit" uniqKey="Singhal A" first="Amit" last="Singhal">Amit Singhal</name>
<affiliation><nlm:affiliation>Singapore Immunology Network, Agency for Science, Technology, and Research.</nlm:affiliation>
<wicri:noCountry code="subField">and Research</wicri:noCountry>
</affiliation>
<affiliation wicri:level="1"><nlm:affiliation>Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore.</nlm:affiliation>
<country xml:lang="fr">Singapour</country>
<wicri:regionArea>Lee Kong Chian School of Medicine, Nanyang Technological University</wicri:regionArea>
<wicri:noRegion>Nanyang Technological University</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Cliff, Jacqueline M" sort="Cliff, Jacqueline M" uniqKey="Cliff J" first="Jacqueline M" last="Cliff">Jacqueline M. Cliff</name>
<affiliation wicri:level="1"><nlm:affiliation>Department of Immunology and Infection, Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, United Kingdom.</nlm:affiliation>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>Department of Immunology and Infection, Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine</wicri:regionArea>
<wicri:noRegion>London School of Hygiene and Tropical Medicine</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Van Crevel, Reinout" sort="Van Crevel, Reinout" uniqKey="Van Crevel R" first="Reinout" last="Van Crevel">Reinout Van Crevel</name>
<affiliation wicri:level="3"><nlm:affiliation>Department of Internal Medicine, Nijmegen.</nlm:affiliation>
<country>Pays-Bas</country>
<placeName><settlement type="city">Nimègue</settlement>
<region type="province" nuts="2">Gueldre</region>
</placeName>
<wicri:orgArea>Department of Internal Medicine</wicri:orgArea>
</affiliation>
<affiliation wicri:level="3"><nlm:affiliation>Radboud Center for Infectious Diseases, Radboud University Medical Center, Nijmegen.</nlm:affiliation>
<country>Pays-Bas</country>
<placeName><settlement type="city">Nimègue</settlement>
<region type="province" nuts="2">Gueldre</region>
</placeName>
<wicri:orgArea>Radboud Center for Infectious Diseases, Radboud University Medical Center</wicri:orgArea>
</affiliation>
</author>
</analytic>
<series><title level="j">The Journal of infectious diseases</title>
<idno type="eISSN">1537-6613</idno>
<imprint><date when="2019" type="published">2019</date>
</imprint>
</series>
</biblStruct>
</sourceDesc>
</fileDesc>
<profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Cell Proliferation (drug effects)</term>
<term>Down-Regulation (drug effects)</term>
<term>Healthy Volunteers (MeSH)</term>
<term>Host-Pathogen Interactions (drug effects)</term>
<term>Humans (MeSH)</term>
<term>Hypoglycemic Agents (pharmacology)</term>
<term>Leukocytes, Mononuclear (drug effects)</term>
<term>Leukocytes, Mononuclear (microbiology)</term>
<term>Metformin (pharmacology)</term>
<term>Monocytes (drug effects)</term>
<term>Monocytes (metabolism)</term>
<term>Mycobacterium tuberculosis (pathogenicity)</term>
<term>Myeloid Cells (drug effects)</term>
<term>Myeloid Cells (metabolism)</term>
<term>Phagocytosis (drug effects)</term>
<term>Reactive Oxygen Species (metabolism)</term>
<term>Signal Transduction (drug effects)</term>
<term>Tuberculosis (metabolism)</term>
<term>Tuberculosis (microbiology)</term>
<term>Up-Regulation (drug effects)</term>
</keywords>
<keywords scheme="KwdFr" xml:lang="fr"><term>Agranulocytes (effets des médicaments et des substances chimiques)</term>
<term>Agranulocytes (microbiologie)</term>
<term>Cellules myéloïdes (effets des médicaments et des substances chimiques)</term>
<term>Cellules myéloïdes (métabolisme)</term>
<term>Espèces réactives de l'oxygène (métabolisme)</term>
<term>Humains (MeSH)</term>
<term>Hypoglycémiants (pharmacologie)</term>
<term>Interactions hôte-pathogène (effets des médicaments et des substances chimiques)</term>
<term>Metformine (pharmacologie)</term>
<term>Monocytes (effets des médicaments et des substances chimiques)</term>
<term>Monocytes (métabolisme)</term>
<term>Mycobacterium tuberculosis (pathogénicité)</term>
<term>Phagocytose (effets des médicaments et des substances chimiques)</term>
<term>Prolifération cellulaire (effets des médicaments et des substances chimiques)</term>
<term>Régulation négative (effets des médicaments et des substances chimiques)</term>
<term>Régulation positive (effets des médicaments et des substances chimiques)</term>
<term>Transduction du signal (effets des médicaments et des substances chimiques)</term>
<term>Tuberculose (microbiologie)</term>
<term>Tuberculose (métabolisme)</term>
<term>Volontaires sains (MeSH)</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Reactive Oxygen Species</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="pharmacology" xml:lang="en"><term>Hypoglycemic Agents</term>
<term>Metformin</term>
</keywords>
<keywords scheme="MESH" qualifier="drug effects" xml:lang="en"><term>Cell Proliferation</term>
<term>Down-Regulation</term>
<term>Host-Pathogen Interactions</term>
<term>Leukocytes, Mononuclear</term>
<term>Monocytes</term>
<term>Myeloid Cells</term>
<term>Phagocytosis</term>
<term>Signal Transduction</term>
<term>Up-Regulation</term>
</keywords>
<keywords scheme="MESH" qualifier="effets des médicaments et des substances chimiques" xml:lang="fr"><term>Agranulocytes</term>
<term>Cellules myéloïdes</term>
<term>Interactions hôte-pathogène</term>
<term>Monocytes</term>
<term>Phagocytose</term>
<term>Prolifération cellulaire</term>
<term>Régulation négative</term>
<term>Régulation positive</term>
<term>Transduction du signal</term>
</keywords>
<keywords scheme="MESH" qualifier="metabolism" xml:lang="en"><term>Monocytes</term>
<term>Myeloid Cells</term>
<term>Tuberculosis</term>
</keywords>
<keywords scheme="MESH" qualifier="microbiologie" xml:lang="fr"><term>Agranulocytes</term>
<term>Tuberculose</term>
</keywords>
<keywords scheme="MESH" qualifier="microbiology" xml:lang="en"><term>Leukocytes, Mononuclear</term>
<term>Tuberculosis</term>
</keywords>
<keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr"><term>Cellules myéloïdes</term>
<term>Espèces réactives de l'oxygène</term>
<term>Monocytes</term>
<term>Tuberculose</term>
</keywords>
<keywords scheme="MESH" qualifier="pathogenicity" xml:lang="en"><term>Mycobacterium tuberculosis</term>
</keywords>
<keywords scheme="MESH" qualifier="pathogénicité" xml:lang="fr"><term>Mycobacterium tuberculosis</term>
</keywords>
<keywords scheme="MESH" qualifier="pharmacologie" xml:lang="fr"><term>Hypoglycémiants</term>
<term>Metformine</term>
</keywords>
<keywords scheme="MESH" xml:lang="en"><term>Healthy Volunteers</term>
<term>Humans</term>
</keywords>
<keywords scheme="MESH" xml:lang="fr"><term>Humains</term>
<term>Volontaires sains</term>
</keywords>
</textClass>
</profileDesc>
</teiHeader>
<front><div type="abstract" xml:lang="en"><p><b>BACKGROUND</b>
</p>
<p>Metformin, the most widely administered diabetes drug, has been proposed as a candidate adjunctive host-directed therapy for tuberculosis, but little is known about its effects on human host responses to Mycobacterium tuberculosis.</p>
</div>
<div type="abstract" xml:lang="en"><p><b>METHODS</b>
</p>
<p>We investigated in vitro and in vivo effects of metformin in humans.</p>
</div>
<div type="abstract" xml:lang="en"><p><b>RESULTS</b>
</p>
<p>Metformin added to peripheral blood mononuclear cells from healthy volunteers enhanced in vitro cellular metabolism while inhibiting the mammalian target of rapamycin targets p70S6K and 4EBP1, with decreased cytokine production and cellular proliferation and increased phagocytosis activity. Metformin administered to healthy human volunteers led to significant downregulation of genes involved in oxidative phosphorylation, mammalian target of rapamycin signaling, and type I interferon response pathways, particularly following stimulation with M. tuberculosis, and upregulation of genes involved in phagocytosis and reactive oxygen species production was increased. These in vivo effects were accompanied by a metformin-induced shift in myeloid cells from classical to nonclassical monocytes. At a functional level, metformin lowered ex vivo production of tumor necrosis factor α, interferon γ, and interleukin 1β but increased phagocytosis activity and reactive oxygen species production.</p>
</div>
<div type="abstract" xml:lang="en"><p><b>CONCLUSION</b>
</p>
<p>Metformin has a range of potentially beneficial effects on cellular metabolism, immune function, and gene transcription involved in innate host responses to M. tuberculosis.</p>
</div>
</front>
</TEI>
<pubmed><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">30753544</PMID>
<DateCompleted><Year>2020</Year>
<Month>02</Month>
<Day>24</Day>
</DateCompleted>
<DateRevised><Year>2020</Year>
<Month>03</Month>
<Day>18</Day>
</DateRevised>
<Article PubModel="Print"><Journal><ISSN IssnType="Electronic">1537-6613</ISSN>
<JournalIssue CitedMedium="Internet"><Volume>220</Volume>
<Issue>1</Issue>
<PubDate><Year>2019</Year>
<Month>06</Month>
<Day>05</Day>
</PubDate>
</JournalIssue>
<Title>The Journal of infectious diseases</Title>
<ISOAbbreviation>J Infect Dis</ISOAbbreviation>
</Journal>
<ArticleTitle>Metformin Alters Human Host Responses to Mycobacterium tuberculosis in Healthy Subjects.</ArticleTitle>
<Pagination><MedlinePgn>139-150</MedlinePgn>
</Pagination>
<ELocationID EIdType="doi" ValidYN="Y">10.1093/infdis/jiz064</ELocationID>
<Abstract><AbstractText Label="BACKGROUND">Metformin, the most widely administered diabetes drug, has been proposed as a candidate adjunctive host-directed therapy for tuberculosis, but little is known about its effects on human host responses to Mycobacterium tuberculosis.</AbstractText>
<AbstractText Label="METHODS">We investigated in vitro and in vivo effects of metformin in humans.</AbstractText>
<AbstractText Label="RESULTS">Metformin added to peripheral blood mononuclear cells from healthy volunteers enhanced in vitro cellular metabolism while inhibiting the mammalian target of rapamycin targets p70S6K and 4EBP1, with decreased cytokine production and cellular proliferation and increased phagocytosis activity. Metformin administered to healthy human volunteers led to significant downregulation of genes involved in oxidative phosphorylation, mammalian target of rapamycin signaling, and type I interferon response pathways, particularly following stimulation with M. tuberculosis, and upregulation of genes involved in phagocytosis and reactive oxygen species production was increased. These in vivo effects were accompanied by a metformin-induced shift in myeloid cells from classical to nonclassical monocytes. At a functional level, metformin lowered ex vivo production of tumor necrosis factor α, interferon γ, and interleukin 1β but increased phagocytosis activity and reactive oxygen species production.</AbstractText>
<AbstractText Label="CONCLUSION">Metformin has a range of potentially beneficial effects on cellular metabolism, immune function, and gene transcription involved in innate host responses to M. tuberculosis.</AbstractText>
<CopyrightInformation>© The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America.</CopyrightInformation>
</Abstract>
<AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Lachmandas</LastName>
<ForeName>Ekta</ForeName>
<Initials>E</Initials>
<AffiliationInfo><Affiliation>Department of Internal Medicine, Nijmegen.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>Radboud Center for Infectious Diseases, Radboud University Medical Center, Nijmegen.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Eckold</LastName>
<ForeName>Clare</ForeName>
<Initials>C</Initials>
<AffiliationInfo><Affiliation>Department of Immunology and Infection, Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, United Kingdom.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Böhme</LastName>
<ForeName>Julia</ForeName>
<Initials>J</Initials>
<AffiliationInfo><Affiliation>Singapore Immunology Network, Agency for Science, Technology, and Research.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Koeken</LastName>
<ForeName>Valerie A C M</ForeName>
<Initials>VACM</Initials>
<AffiliationInfo><Affiliation>Department of Internal Medicine, Nijmegen.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>Radboud Center for Infectious Diseases, Radboud University Medical Center, Nijmegen.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Marzuki</LastName>
<ForeName>Mardiana Binte</ForeName>
<Initials>MB</Initials>
<AffiliationInfo><Affiliation>Singapore Immunology Network, Agency for Science, Technology, and Research.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Blok</LastName>
<ForeName>Bastiaan</ForeName>
<Initials>B</Initials>
<AffiliationInfo><Affiliation>Department of Internal Medicine, Nijmegen.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>Radboud Center for Infectious Diseases, Radboud University Medical Center, Nijmegen.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Arts</LastName>
<ForeName>Rob J W</ForeName>
<Initials>RJW</Initials>
<AffiliationInfo><Affiliation>Department of Internal Medicine, Nijmegen.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>Radboud Center for Infectious Diseases, Radboud University Medical Center, Nijmegen.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Chen</LastName>
<ForeName>Jinmiao</ForeName>
<Initials>J</Initials>
<AffiliationInfo><Affiliation>Singapore Immunology Network, Agency for Science, Technology, and Research.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Teng</LastName>
<ForeName>Karen W W</ForeName>
<Initials>KWW</Initials>
<AffiliationInfo><Affiliation>Singapore Immunology Network, Agency for Science, Technology, and Research.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Ratter</LastName>
<ForeName>Jacqueline</ForeName>
<Initials>J</Initials>
<AffiliationInfo><Affiliation>Department of Internal Medicine, Nijmegen.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>Radboud Center for Infectious Diseases, Radboud University Medical Center, Nijmegen.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>Nutrition, Metabolism and Genomics Group, Division of Human Nutrition, Wageningen University, Wageningen, the Netherlands.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Smolders</LastName>
<ForeName>Elise J</ForeName>
<Initials>EJ</Initials>
<AffiliationInfo><Affiliation>Department of Internal Medicine, Nijmegen.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>Radboud Center for Infectious Diseases, Radboud University Medical Center, Nijmegen.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Van den Heuvel</LastName>
<ForeName>Corina</ForeName>
<Initials>C</Initials>
<AffiliationInfo><Affiliation>Department of Internal Medicine, Nijmegen.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>Radboud Center for Infectious Diseases, Radboud University Medical Center, Nijmegen.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Stienstra</LastName>
<ForeName>Rinke</ForeName>
<Initials>R</Initials>
<AffiliationInfo><Affiliation>Department of Internal Medicine, Nijmegen.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>Radboud Center for Infectious Diseases, Radboud University Medical Center, Nijmegen.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>Nutrition, Metabolism and Genomics Group, Division of Human Nutrition, Wageningen University, Wageningen, the Netherlands.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Dockrell</LastName>
<ForeName>Hazel M</ForeName>
<Initials>HM</Initials>
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   |flux=    Main
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   |type=    RBID
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   |texte=   Metformin Alters Human Host Responses to Mycobacterium tuberculosis in Healthy Subjects.
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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

Metformin Alters Human Host Responses to Mycobacterium tuberculosis in Healthy Subjects.

Metformin Alters Human Host Responses to Mycobacterium tuberculosis in Healthy Subjects.

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