RapamycinFungusV1, Main, Exploration, bibRecord, 000301

Leptin signaling impairs macrophage defenses against Salmonella Typhimurium.

Identifieur interne : 000301 ( Main/Exploration ); précédent : 000300; suivant : 000302

Leptin signaling impairs macrophage defenses against Salmonella Typhimurium.

Auteurs : Julia Fischer [Allemagne] ; Saray Gutièrrez [Allemagne] ; Raja Ganesan [Australie] ; Chiara Calabrese [Allemagne] ; Rajeev Ranjan [Allemagne] ; Gökhan Cildir [Australie] ; Nina Judith Hos [Allemagne] ; Jan Rybniker [Allemagne] ; Martina Wolke [Allemagne] ; Jochen W U. Fries [Allemagne] ; Vinay Tergaonkar [Australie, Singapour] ; Georg Plum [Allemagne] ; Adam Antebi [Allemagne] ; Nirmal Robinson [Australie, Allemagne]

Source :

Proceedings of the National Academy of Sciences of the United States of America [ 1091-6490 ] ; 2019.

RBID : pubmed:31350351

Descripteurs français

KwdFr :
- Adulte (MeSH), Animaux (MeSH), Cellules RAW 264.7 (MeSH), Complexe-2 cible mécanistique de la rapamycine (métabolisme), Femelle (MeSH), Humains (MeSH), Inflammation (anatomopathologie), Jeune adulte (MeSH), Leptine (antagonistes et inhibiteurs), Leptine (métabolisme), Lysosomes (métabolisme), Macrophages (immunologie), Macrophages (microbiologie), Modèles biologiques (MeSH), Phagosomes (métabolisme), Phosphoprotein Phosphatases (métabolisme), Phosphorylation (MeSH), Protéines proto-oncogènes c-akt (métabolisme), Récepteurs à la leptine (métabolisme), Salmonella typhimurium (immunologie), Salmonelloses animales (MeSH), Souris (MeSH), Souris de lignée C57BL (MeSH), Transduction du signal (MeSH).
MESH :
- anatomopathologie : Inflammation.
- antagonistes et inhibiteurs : Leptine.
- immunologie : Macrophages, Salmonella typhimurium.
- microbiologie : Macrophages.
- métabolisme : Complexe-2 cible mécanistique de la rapamycine, Leptine, Lysosomes, Phagosomes, Phosphoprotein Phosphatases, Protéines proto-oncogènes c-akt, Récepteurs à la leptine.
- Adulte, Animaux, Cellules RAW 264.7, Femelle, Humains, Jeune adulte, Modèles biologiques, Phosphorylation, Salmonelloses animales, Souris, Souris de lignée C57BL, Transduction du signal.

English descriptors

KwdEn :
- Adult (MeSH), Animals (MeSH), Female (MeSH), Humans (MeSH), Inflammation (pathology), Leptin (antagonists & inhibitors), Leptin (metabolism), Lysosomes (metabolism), Macrophages (immunology), Macrophages (microbiology), Mechanistic Target of Rapamycin Complex 2 (metabolism), Mice (MeSH), Mice, Inbred C57BL (MeSH), Models, Biological (MeSH), Phagosomes (metabolism), Phosphoprotein Phosphatases (metabolism), Phosphorylation (MeSH), Proto-Oncogene Proteins c-akt (metabolism), RAW 264.7 Cells (MeSH), Receptors, Leptin (metabolism), Salmonella Infections, Animal (MeSH), Salmonella typhimurium (immunology), Signal Transduction (MeSH), Young Adult (MeSH).
MESH :
- chemical , antagonists & inhibitors : Leptin.
- chemical , metabolism : Leptin, Mechanistic Target of Rapamycin Complex 2, Phosphoprotein Phosphatases, Proto-Oncogene Proteins c-akt, Receptors, Leptin.
- immunology : Macrophages, Salmonella typhimurium.
- metabolism : Lysosomes, Phagosomes.
- microbiology : Macrophages.
- pathology : Inflammation.
- Adult, Animals, Female, Humans, Mice, Mice, Inbred C57BL, Models, Biological, Phosphorylation, RAW 264.7 Cells, Salmonella Infections, Animal, Signal Transduction, Young Adult.

Abstract

The dynamic interplay between metabolism and immune responses in health and disease, by which different immune cells impact on metabolic processes, are being increasingly appreciated. However, the potential of master regulators of metabolism to control innate immunity are less understood. Here, we studied the cross-talk between leptin signaling and macrophage function in the context of bacterial infections. We found that upon infection with Gram-negative pathogens, such as Salmonella Typhimurium, leptin receptor (Lepr) expression increased in both mouse and human macrophages. Unexpectedly, both genetic Lepr ablation in macrophages and global pharmacologic leptin antagonization augmented lysosomal functions, reduced S Typhimurium burden, and diminished inflammation in vitro and in vivo. Mechanistically, we show that leptin induction activates the mTORC2/Akt pathway and subsequently down-regulates Phlpp1 phosphatase, allowing for phosphorylated Akt to impair lysosomal-mediated pathogen clearance. These data highlight a link between leptin signaling, the mTORC2/Phlpp1/Akt axis, and lysosomal activity in macrophages and have important therapeutic implications for modulating innate immunity to combat Gram-negative bacterial infections.

DOI: 10.1073/pnas.1904885116
PubMed: 31350351
PubMed Central: PMC6697794

Affiliations:

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Le document en format XML

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<author><name sortKey="Hos, Nina Judith" sort="Hos, Nina Judith" uniqKey="Hos N" first="Nina Judith" last="Hos">Nina Judith Hos</name>
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<author><name sortKey="Rybniker, Jan" sort="Rybniker, Jan" uniqKey="Rybniker J" first="Jan" last="Rybniker">Jan Rybniker</name>
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<affiliation wicri:level="3"><nlm:affiliation>Partner Site Bonn-Cologne, German Center for Infection Research (DZIF), D-50931 Cologne, Germany.</nlm:affiliation>
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<affiliation wicri:level="3"><nlm:affiliation>Center for Molecular Medicine Cologne, University of Cologne, 50931 Cologne, Germany.</nlm:affiliation>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Center for Molecular Medicine Cologne, University of Cologne, 50931 Cologne</wicri:regionArea>
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<affiliation wicri:level="3"><nlm:affiliation>Institute for Medical Microbiology, Immunology and Hygiene, University of Cologne, 50935 Cologne, Germany.</nlm:affiliation>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Institute for Medical Microbiology, Immunology and Hygiene, University of Cologne, 50935 Cologne</wicri:regionArea>
<placeName><region type="land" nuts="1">Rhénanie-du-Nord-Westphalie</region>
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<author><name sortKey="Wolke, Martina" sort="Wolke, Martina" uniqKey="Wolke M" first="Martina" last="Wolke">Martina Wolke</name>
<affiliation wicri:level="3"><nlm:affiliation>Institute for Medical Microbiology, Immunology and Hygiene, University of Cologne, 50935 Cologne, Germany.</nlm:affiliation>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Institute for Medical Microbiology, Immunology and Hygiene, University of Cologne, 50935 Cologne</wicri:regionArea>
<placeName><region type="land" nuts="1">Rhénanie-du-Nord-Westphalie</region>
<region type="district" nuts="2">District de Cologne</region>
<settlement type="city">Cologne</settlement>
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</author>
<author><name sortKey="Fries, Jochen W U" sort="Fries, Jochen W U" uniqKey="Fries J" first="Jochen W U" last="Fries">Jochen W U. Fries</name>
<affiliation wicri:level="3"><nlm:affiliation>Institute of Pathology, University of Cologne, D-50931 Cologne, Germany.</nlm:affiliation>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Institute of Pathology, University of Cologne, D-50931 Cologne</wicri:regionArea>
<placeName><region type="land" nuts="1">Rhénanie-du-Nord-Westphalie</region>
<region type="district" nuts="2">District de Cologne</region>
<settlement type="city">Cologne</settlement>
</placeName>
</affiliation>
</author>
<author><name sortKey="Tergaonkar, Vinay" sort="Tergaonkar, Vinay" uniqKey="Tergaonkar V" first="Vinay" last="Tergaonkar">Vinay Tergaonkar</name>
<affiliation wicri:level="1"><nlm:affiliation>Center for Cancer Biology, University of South Australia and SA Pathology, Adelaide SA 5001, Australia.</nlm:affiliation>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>Center for Cancer Biology, University of South Australia and SA Pathology, Adelaide SA 5001</wicri:regionArea>
<wicri:noRegion>Adelaide SA 5001</wicri:noRegion>
</affiliation>
<affiliation wicri:level="1"><nlm:affiliation>Laboratory of NF-κB Signaling, Institute of Molecular and Cell Biology, Proteos, 138673 Singapore, Singapore.</nlm:affiliation>
<country xml:lang="fr">Singapour</country>
<wicri:regionArea>Laboratory of NF-κB Signaling, Institute of Molecular and Cell Biology, Proteos, 138673 Singapore</wicri:regionArea>
<wicri:noRegion>138673 Singapore</wicri:noRegion>
</affiliation>
<affiliation wicri:level="4"><nlm:affiliation>Department of Biochemistry, National University of Singapore (NUS), 117597 Singapore.</nlm:affiliation>
<country xml:lang="fr">Singapour</country>
<wicri:regionArea>Department of Biochemistry, National University of Singapore (NUS)</wicri:regionArea>
<orgName type="university">Université nationale de Singapour</orgName>
</affiliation>
<affiliation wicri:level="1"><nlm:affiliation>Department of Pathology, Yong Loo Lin School of Medicine, NUS, 117597 Singapore.</nlm:affiliation>
<country xml:lang="fr">Singapour</country>
<wicri:regionArea>Department of Pathology, Yong Loo Lin School of Medicine, NUS</wicri:regionArea>
<wicri:noRegion>NUS</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Plum, Georg" sort="Plum, Georg" uniqKey="Plum G" first="Georg" last="Plum">Georg Plum</name>
<affiliation wicri:level="3"><nlm:affiliation>Institute for Medical Microbiology, Immunology and Hygiene, University of Cologne, 50935 Cologne, Germany.</nlm:affiliation>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Institute for Medical Microbiology, Immunology and Hygiene, University of Cologne, 50935 Cologne</wicri:regionArea>
<placeName><region type="land" nuts="1">Rhénanie-du-Nord-Westphalie</region>
<region type="district" nuts="2">District de Cologne</region>
<settlement type="city">Cologne</settlement>
</placeName>
</affiliation>
</author>
<author><name sortKey="Antebi, Adam" sort="Antebi, Adam" uniqKey="Antebi A" first="Adam" last="Antebi">Adam Antebi</name>
<affiliation wicri:level="3"><nlm:affiliation>Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, 50931 Cologne, Germany.</nlm:affiliation>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, 50931 Cologne</wicri:regionArea>
<placeName><region type="land" nuts="1">Rhénanie-du-Nord-Westphalie</region>
<region type="district" nuts="2">District de Cologne</region>
<settlement type="city">Cologne</settlement>
</placeName>
</affiliation>
<affiliation wicri:level="3"><nlm:affiliation>Molecular Genetics of Ageing Laboratory, Max Planck Institute for Biology of Ageing, 50931 Cologne, Germany.</nlm:affiliation>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Molecular Genetics of Ageing Laboratory, Max Planck Institute for Biology of Ageing, 50931 Cologne</wicri:regionArea>
<placeName><region type="land" nuts="1">Rhénanie-du-Nord-Westphalie</region>
<region type="district" nuts="2">District de Cologne</region>
<settlement type="city">Cologne</settlement>
</placeName>
</affiliation>
</author>
<author><name sortKey="Robinson, Nirmal" sort="Robinson, Nirmal" uniqKey="Robinson N" first="Nirmal" last="Robinson">Nirmal Robinson</name>
<affiliation wicri:level="1"><nlm:affiliation>Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, 50931 Cologne, Germany; nirmal.robinson@unisa.edu.au.</nlm:affiliation>
<country wicri:rule="url">Australie</country>
<wicri:regionArea>Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, 50931 Cologne</wicri:regionArea>
<wicri:noRegion>50931 Cologne</wicri:noRegion>
</affiliation>
<affiliation wicri:level="3"><nlm:affiliation>Institute for Medical Microbiology, Immunology and Hygiene, University of Cologne, 50935 Cologne, Germany.</nlm:affiliation>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Institute for Medical Microbiology, Immunology and Hygiene, University of Cologne, 50935 Cologne</wicri:regionArea>
<placeName><region type="land" nuts="1">Rhénanie-du-Nord-Westphalie</region>
<region type="district" nuts="2">District de Cologne</region>
<settlement type="city">Cologne</settlement>
</placeName>
</affiliation>
<affiliation wicri:level="1"><nlm:affiliation>Center for Cancer Biology, University of South Australia and SA Pathology, Adelaide SA 5001, Australia.</nlm:affiliation>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>Center for Cancer Biology, University of South Australia and SA Pathology, Adelaide SA 5001</wicri:regionArea>
<wicri:noRegion>Adelaide SA 5001</wicri:noRegion>
</affiliation>
</author>
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<sourceDesc><biblStruct><analytic><title xml:lang="en">Leptin signaling impairs macrophage defenses against <i>Salmonella</i>
 Typhimurium.</title>
<author><name sortKey="Fischer, Julia" sort="Fischer, Julia" uniqKey="Fischer J" first="Julia" last="Fischer">Julia Fischer</name>
<affiliation wicri:level="3"><nlm:affiliation>Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, 50931 Cologne, Germany.</nlm:affiliation>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, 50931 Cologne</wicri:regionArea>
<placeName><region type="land" nuts="1">Rhénanie-du-Nord-Westphalie</region>
<region type="district" nuts="2">District de Cologne</region>
<settlement type="city">Cologne</settlement>
</placeName>
</affiliation>
<affiliation wicri:level="3"><nlm:affiliation>Department I of Internal Medicine, University of Cologne, D-50937 Cologne, Germany.</nlm:affiliation>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Department I of Internal Medicine, University of Cologne, D-50937 Cologne</wicri:regionArea>
<placeName><region type="land" nuts="1">Rhénanie-du-Nord-Westphalie</region>
<region type="district" nuts="2">District de Cologne</region>
<settlement type="city">Cologne</settlement>
</placeName>
</affiliation>
<affiliation wicri:level="3"><nlm:affiliation>Division of Infectious Diseases, University of Cologne, D-50937 Cologne, Germany.</nlm:affiliation>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Division of Infectious Diseases, University of Cologne, D-50937 Cologne</wicri:regionArea>
<placeName><region type="land" nuts="1">Rhénanie-du-Nord-Westphalie</region>
<region type="district" nuts="2">District de Cologne</region>
<settlement type="city">Cologne</settlement>
</placeName>
</affiliation>
<affiliation wicri:level="3"><nlm:affiliation>Partner Site Bonn-Cologne, German Center for Infection Research (DZIF), D-50931 Cologne, Germany.</nlm:affiliation>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Partner Site Bonn-Cologne, German Center for Infection Research (DZIF), D-50931 Cologne</wicri:regionArea>
<placeName><region type="land" nuts="1">Rhénanie-du-Nord-Westphalie</region>
<region type="district" nuts="2">District de Cologne</region>
<settlement type="city">Cologne</settlement>
</placeName>
</affiliation>
<affiliation wicri:level="3"><nlm:affiliation>Center for Molecular Medicine Cologne, University of Cologne, 50931 Cologne, Germany.</nlm:affiliation>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Center for Molecular Medicine Cologne, University of Cologne, 50931 Cologne</wicri:regionArea>
<placeName><region type="land" nuts="1">Rhénanie-du-Nord-Westphalie</region>
<region type="district" nuts="2">District de Cologne</region>
<settlement type="city">Cologne</settlement>
</placeName>
</affiliation>
</author>
<author><name sortKey="Gutierrez, Saray" sort="Gutierrez, Saray" uniqKey="Gutierrez S" first="Saray" last="Gutièrrez">Saray Gutièrrez</name>
<affiliation wicri:level="3"><nlm:affiliation>Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, 50931 Cologne, Germany.</nlm:affiliation>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, 50931 Cologne</wicri:regionArea>
<placeName><region type="land" nuts="1">Rhénanie-du-Nord-Westphalie</region>
<region type="district" nuts="2">District de Cologne</region>
<settlement type="city">Cologne</settlement>
</placeName>
</affiliation>
<affiliation wicri:level="3"><nlm:affiliation>Institute for Medical Microbiology, Immunology and Hygiene, University of Cologne, 50935 Cologne, Germany.</nlm:affiliation>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Institute for Medical Microbiology, Immunology and Hygiene, University of Cologne, 50935 Cologne</wicri:regionArea>
<placeName><region type="land" nuts="1">Rhénanie-du-Nord-Westphalie</region>
<region type="district" nuts="2">District de Cologne</region>
<settlement type="city">Cologne</settlement>
</placeName>
</affiliation>
</author>
<author><name sortKey="Ganesan, Raja" sort="Ganesan, Raja" uniqKey="Ganesan R" first="Raja" last="Ganesan">Raja Ganesan</name>
<affiliation wicri:level="1"><nlm:affiliation>Center for Cancer Biology, University of South Australia and SA Pathology, Adelaide SA 5001, Australia.</nlm:affiliation>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>Center for Cancer Biology, University of South Australia and SA Pathology, Adelaide SA 5001</wicri:regionArea>
<wicri:noRegion>Adelaide SA 5001</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Calabrese, Chiara" sort="Calabrese, Chiara" uniqKey="Calabrese C" first="Chiara" last="Calabrese">Chiara Calabrese</name>
<affiliation wicri:level="3"><nlm:affiliation>Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, 50931 Cologne, Germany.</nlm:affiliation>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, 50931 Cologne</wicri:regionArea>
<placeName><region type="land" nuts="1">Rhénanie-du-Nord-Westphalie</region>
<region type="district" nuts="2">District de Cologne</region>
<settlement type="city">Cologne</settlement>
</placeName>
</affiliation>
</author>
<author><name sortKey="Ranjan, Rajeev" sort="Ranjan, Rajeev" uniqKey="Ranjan R" first="Rajeev" last="Ranjan">Rajeev Ranjan</name>
<affiliation wicri:level="3"><nlm:affiliation>Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, 50931 Cologne, Germany.</nlm:affiliation>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, 50931 Cologne</wicri:regionArea>
<placeName><region type="land" nuts="1">Rhénanie-du-Nord-Westphalie</region>
<region type="district" nuts="2">District de Cologne</region>
<settlement type="city">Cologne</settlement>
</placeName>
</affiliation>
</author>
<author><name sortKey="Cildir, Gokhan" sort="Cildir, Gokhan" uniqKey="Cildir G" first="Gökhan" last="Cildir">Gökhan Cildir</name>
<affiliation wicri:level="1"><nlm:affiliation>Center for Cancer Biology, University of South Australia and SA Pathology, Adelaide SA 5001, Australia.</nlm:affiliation>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>Center for Cancer Biology, University of South Australia and SA Pathology, Adelaide SA 5001</wicri:regionArea>
<wicri:noRegion>Adelaide SA 5001</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Hos, Nina Judith" sort="Hos, Nina Judith" uniqKey="Hos N" first="Nina Judith" last="Hos">Nina Judith Hos</name>
<affiliation wicri:level="3"><nlm:affiliation>Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, 50931 Cologne, Germany.</nlm:affiliation>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, 50931 Cologne</wicri:regionArea>
<placeName><region type="land" nuts="1">Rhénanie-du-Nord-Westphalie</region>
<region type="district" nuts="2">District de Cologne</region>
<settlement type="city">Cologne</settlement>
</placeName>
</affiliation>
<affiliation wicri:level="3"><nlm:affiliation>Partner Site Bonn-Cologne, German Center for Infection Research (DZIF), D-50931 Cologne, Germany.</nlm:affiliation>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Partner Site Bonn-Cologne, German Center for Infection Research (DZIF), D-50931 Cologne</wicri:regionArea>
<placeName><region type="land" nuts="1">Rhénanie-du-Nord-Westphalie</region>
<region type="district" nuts="2">District de Cologne</region>
<settlement type="city">Cologne</settlement>
</placeName>
</affiliation>
<affiliation wicri:level="3"><nlm:affiliation>Institute for Medical Microbiology, Immunology and Hygiene, University of Cologne, 50935 Cologne, Germany.</nlm:affiliation>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Institute for Medical Microbiology, Immunology and Hygiene, University of Cologne, 50935 Cologne</wicri:regionArea>
<placeName><region type="land" nuts="1">Rhénanie-du-Nord-Westphalie</region>
<region type="district" nuts="2">District de Cologne</region>
<settlement type="city">Cologne</settlement>
</placeName>
</affiliation>
</author>
<author><name sortKey="Rybniker, Jan" sort="Rybniker, Jan" uniqKey="Rybniker J" first="Jan" last="Rybniker">Jan Rybniker</name>
<affiliation wicri:level="3"><nlm:affiliation>Department I of Internal Medicine, University of Cologne, D-50937 Cologne, Germany.</nlm:affiliation>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Department I of Internal Medicine, University of Cologne, D-50937 Cologne</wicri:regionArea>
<placeName><region type="land" nuts="1">Rhénanie-du-Nord-Westphalie</region>
<region type="district" nuts="2">District de Cologne</region>
<settlement type="city">Cologne</settlement>
</placeName>
</affiliation>
<affiliation wicri:level="3"><nlm:affiliation>Division of Infectious Diseases, University of Cologne, D-50937 Cologne, Germany.</nlm:affiliation>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Division of Infectious Diseases, University of Cologne, D-50937 Cologne</wicri:regionArea>
<placeName><region type="land" nuts="1">Rhénanie-du-Nord-Westphalie</region>
<region type="district" nuts="2">District de Cologne</region>
<settlement type="city">Cologne</settlement>
</placeName>
</affiliation>
<affiliation wicri:level="3"><nlm:affiliation>Partner Site Bonn-Cologne, German Center for Infection Research (DZIF), D-50931 Cologne, Germany.</nlm:affiliation>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Partner Site Bonn-Cologne, German Center for Infection Research (DZIF), D-50931 Cologne</wicri:regionArea>
<placeName><region type="land" nuts="1">Rhénanie-du-Nord-Westphalie</region>
<region type="district" nuts="2">District de Cologne</region>
<settlement type="city">Cologne</settlement>
</placeName>
</affiliation>
<affiliation wicri:level="3"><nlm:affiliation>Center for Molecular Medicine Cologne, University of Cologne, 50931 Cologne, Germany.</nlm:affiliation>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Center for Molecular Medicine Cologne, University of Cologne, 50931 Cologne</wicri:regionArea>
<placeName><region type="land" nuts="1">Rhénanie-du-Nord-Westphalie</region>
<region type="district" nuts="2">District de Cologne</region>
<settlement type="city">Cologne</settlement>
</placeName>
</affiliation>
<affiliation wicri:level="3"><nlm:affiliation>Institute for Medical Microbiology, Immunology and Hygiene, University of Cologne, 50935 Cologne, Germany.</nlm:affiliation>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Institute for Medical Microbiology, Immunology and Hygiene, University of Cologne, 50935 Cologne</wicri:regionArea>
<placeName><region type="land" nuts="1">Rhénanie-du-Nord-Westphalie</region>
<region type="district" nuts="2">District de Cologne</region>
<settlement type="city">Cologne</settlement>
</placeName>
</affiliation>
</author>
<author><name sortKey="Wolke, Martina" sort="Wolke, Martina" uniqKey="Wolke M" first="Martina" last="Wolke">Martina Wolke</name>
<affiliation wicri:level="3"><nlm:affiliation>Institute for Medical Microbiology, Immunology and Hygiene, University of Cologne, 50935 Cologne, Germany.</nlm:affiliation>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Institute for Medical Microbiology, Immunology and Hygiene, University of Cologne, 50935 Cologne</wicri:regionArea>
<placeName><region type="land" nuts="1">Rhénanie-du-Nord-Westphalie</region>
<region type="district" nuts="2">District de Cologne</region>
<settlement type="city">Cologne</settlement>
</placeName>
</affiliation>
</author>
<author><name sortKey="Fries, Jochen W U" sort="Fries, Jochen W U" uniqKey="Fries J" first="Jochen W U" last="Fries">Jochen W U. Fries</name>
<affiliation wicri:level="3"><nlm:affiliation>Institute of Pathology, University of Cologne, D-50931 Cologne, Germany.</nlm:affiliation>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Institute of Pathology, University of Cologne, D-50931 Cologne</wicri:regionArea>
<placeName><region type="land" nuts="1">Rhénanie-du-Nord-Westphalie</region>
<region type="district" nuts="2">District de Cologne</region>
<settlement type="city">Cologne</settlement>
</placeName>
</affiliation>
</author>
<author><name sortKey="Tergaonkar, Vinay" sort="Tergaonkar, Vinay" uniqKey="Tergaonkar V" first="Vinay" last="Tergaonkar">Vinay Tergaonkar</name>
<affiliation wicri:level="1"><nlm:affiliation>Center for Cancer Biology, University of South Australia and SA Pathology, Adelaide SA 5001, Australia.</nlm:affiliation>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>Center for Cancer Biology, University of South Australia and SA Pathology, Adelaide SA 5001</wicri:regionArea>
<wicri:noRegion>Adelaide SA 5001</wicri:noRegion>
</affiliation>
<affiliation wicri:level="1"><nlm:affiliation>Laboratory of NF-κB Signaling, Institute of Molecular and Cell Biology, Proteos, 138673 Singapore, Singapore.</nlm:affiliation>
<country xml:lang="fr">Singapour</country>
<wicri:regionArea>Laboratory of NF-κB Signaling, Institute of Molecular and Cell Biology, Proteos, 138673 Singapore</wicri:regionArea>
<wicri:noRegion>138673 Singapore</wicri:noRegion>
</affiliation>
<affiliation wicri:level="4"><nlm:affiliation>Department of Biochemistry, National University of Singapore (NUS), 117597 Singapore.</nlm:affiliation>
<country xml:lang="fr">Singapour</country>
<wicri:regionArea>Department of Biochemistry, National University of Singapore (NUS)</wicri:regionArea>
<orgName type="university">Université nationale de Singapour</orgName>
</affiliation>
<affiliation wicri:level="1"><nlm:affiliation>Department of Pathology, Yong Loo Lin School of Medicine, NUS, 117597 Singapore.</nlm:affiliation>
<country xml:lang="fr">Singapour</country>
<wicri:regionArea>Department of Pathology, Yong Loo Lin School of Medicine, NUS</wicri:regionArea>
<wicri:noRegion>NUS</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Plum, Georg" sort="Plum, Georg" uniqKey="Plum G" first="Georg" last="Plum">Georg Plum</name>
<affiliation wicri:level="3"><nlm:affiliation>Institute for Medical Microbiology, Immunology and Hygiene, University of Cologne, 50935 Cologne, Germany.</nlm:affiliation>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Institute for Medical Microbiology, Immunology and Hygiene, University of Cologne, 50935 Cologne</wicri:regionArea>
<placeName><region type="land" nuts="1">Rhénanie-du-Nord-Westphalie</region>
<region type="district" nuts="2">District de Cologne</region>
<settlement type="city">Cologne</settlement>
</placeName>
</affiliation>
</author>
<author><name sortKey="Antebi, Adam" sort="Antebi, Adam" uniqKey="Antebi A" first="Adam" last="Antebi">Adam Antebi</name>
<affiliation wicri:level="3"><nlm:affiliation>Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, 50931 Cologne, Germany.</nlm:affiliation>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, 50931 Cologne</wicri:regionArea>
<placeName><region type="land" nuts="1">Rhénanie-du-Nord-Westphalie</region>
<region type="district" nuts="2">District de Cologne</region>
<settlement type="city">Cologne</settlement>
</placeName>
</affiliation>
<affiliation wicri:level="3"><nlm:affiliation>Molecular Genetics of Ageing Laboratory, Max Planck Institute for Biology of Ageing, 50931 Cologne, Germany.</nlm:affiliation>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Molecular Genetics of Ageing Laboratory, Max Planck Institute for Biology of Ageing, 50931 Cologne</wicri:regionArea>
<placeName><region type="land" nuts="1">Rhénanie-du-Nord-Westphalie</region>
<region type="district" nuts="2">District de Cologne</region>
<settlement type="city">Cologne</settlement>
</placeName>
</affiliation>
</author>
<author><name sortKey="Robinson, Nirmal" sort="Robinson, Nirmal" uniqKey="Robinson N" first="Nirmal" last="Robinson">Nirmal Robinson</name>
<affiliation wicri:level="1"><nlm:affiliation>Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, 50931 Cologne, Germany; nirmal.robinson@unisa.edu.au.</nlm:affiliation>
<country wicri:rule="url">Australie</country>
<wicri:regionArea>Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, 50931 Cologne</wicri:regionArea>
<wicri:noRegion>50931 Cologne</wicri:noRegion>
</affiliation>
<affiliation wicri:level="3"><nlm:affiliation>Institute for Medical Microbiology, Immunology and Hygiene, University of Cologne, 50935 Cologne, Germany.</nlm:affiliation>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Institute for Medical Microbiology, Immunology and Hygiene, University of Cologne, 50935 Cologne</wicri:regionArea>
<placeName><region type="land" nuts="1">Rhénanie-du-Nord-Westphalie</region>
<region type="district" nuts="2">District de Cologne</region>
<settlement type="city">Cologne</settlement>
</placeName>
</affiliation>
<affiliation wicri:level="1"><nlm:affiliation>Center for Cancer Biology, University of South Australia and SA Pathology, Adelaide SA 5001, Australia.</nlm:affiliation>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>Center for Cancer Biology, University of South Australia and SA Pathology, Adelaide SA 5001</wicri:regionArea>
<wicri:noRegion>Adelaide SA 5001</wicri:noRegion>
</affiliation>
</author>
</analytic>
<series><title level="j">Proceedings of the National Academy of Sciences of the United States of America</title>
<idno type="eISSN">1091-6490</idno>
<imprint><date when="2019" type="published">2019</date>
</imprint>
</series>
</biblStruct>
</sourceDesc>
</fileDesc>
<profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Adult (MeSH)</term>
<term>Animals (MeSH)</term>
<term>Female (MeSH)</term>
<term>Humans (MeSH)</term>
<term>Inflammation (pathology)</term>
<term>Leptin (antagonists & inhibitors)</term>
<term>Leptin (metabolism)</term>
<term>Lysosomes (metabolism)</term>
<term>Macrophages (immunology)</term>
<term>Macrophages (microbiology)</term>
<term>Mechanistic Target of Rapamycin Complex 2 (metabolism)</term>
<term>Mice (MeSH)</term>
<term>Mice, Inbred C57BL (MeSH)</term>
<term>Models, Biological (MeSH)</term>
<term>Phagosomes (metabolism)</term>
<term>Phosphoprotein Phosphatases (metabolism)</term>
<term>Phosphorylation (MeSH)</term>
<term>Proto-Oncogene Proteins c-akt (metabolism)</term>
<term>RAW 264.7 Cells (MeSH)</term>
<term>Receptors, Leptin (metabolism)</term>
<term>Salmonella Infections, Animal (MeSH)</term>
<term>Salmonella typhimurium (immunology)</term>
<term>Signal Transduction (MeSH)</term>
<term>Young Adult (MeSH)</term>
</keywords>
<keywords scheme="KwdFr" xml:lang="fr"><term>Adulte (MeSH)</term>
<term>Animaux (MeSH)</term>
<term>Cellules RAW 264.7 (MeSH)</term>
<term>Complexe-2 cible mécanistique de la rapamycine (métabolisme)</term>
<term>Femelle (MeSH)</term>
<term>Humains (MeSH)</term>
<term>Inflammation (anatomopathologie)</term>
<term>Jeune adulte (MeSH)</term>
<term>Leptine (antagonistes et inhibiteurs)</term>
<term>Leptine (métabolisme)</term>
<term>Lysosomes (métabolisme)</term>
<term>Macrophages (immunologie)</term>
<term>Macrophages (microbiologie)</term>
<term>Modèles biologiques (MeSH)</term>
<term>Phagosomes (métabolisme)</term>
<term>Phosphoprotein Phosphatases (métabolisme)</term>
<term>Phosphorylation (MeSH)</term>
<term>Protéines proto-oncogènes c-akt (métabolisme)</term>
<term>Récepteurs à la leptine (métabolisme)</term>
<term>Salmonella typhimurium (immunologie)</term>
<term>Salmonelloses animales (MeSH)</term>
<term>Souris (MeSH)</term>
<term>Souris de lignée C57BL (MeSH)</term>
<term>Transduction du signal (MeSH)</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="antagonists & inhibitors" xml:lang="en"><term>Leptin</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Leptin</term>
<term>Mechanistic Target of Rapamycin Complex 2</term>
<term>Phosphoprotein Phosphatases</term>
<term>Proto-Oncogene Proteins c-akt</term>
<term>Receptors, Leptin</term>
</keywords>
<keywords scheme="MESH" qualifier="anatomopathologie" xml:lang="fr"><term>Inflammation</term>
</keywords>
<keywords scheme="MESH" qualifier="antagonistes et inhibiteurs" xml:lang="fr"><term>Leptine</term>
</keywords>
<keywords scheme="MESH" qualifier="immunologie" xml:lang="fr"><term>Macrophages</term>
<term>Salmonella typhimurium</term>
</keywords>
<keywords scheme="MESH" qualifier="immunology" xml:lang="en"><term>Macrophages</term>
<term>Salmonella typhimurium</term>
</keywords>
<keywords scheme="MESH" qualifier="metabolism" xml:lang="en"><term>Lysosomes</term>
<term>Phagosomes</term>
</keywords>
<keywords scheme="MESH" qualifier="microbiologie" xml:lang="fr"><term>Macrophages</term>
</keywords>
<keywords scheme="MESH" qualifier="microbiology" xml:lang="en"><term>Macrophages</term>
</keywords>
<keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr"><term>Complexe-2 cible mécanistique de la rapamycine</term>
<term>Leptine</term>
<term>Lysosomes</term>
<term>Phagosomes</term>
<term>Phosphoprotein Phosphatases</term>
<term>Protéines proto-oncogènes c-akt</term>
<term>Récepteurs à la leptine</term>
</keywords>
<keywords scheme="MESH" qualifier="pathology" xml:lang="en"><term>Inflammation</term>
</keywords>
<keywords scheme="MESH" xml:lang="en"><term>Adult</term>
<term>Animals</term>
<term>Female</term>
<term>Humans</term>
<term>Mice</term>
<term>Mice, Inbred C57BL</term>
<term>Models, Biological</term>
<term>Phosphorylation</term>
<term>RAW 264.7 Cells</term>
<term>Salmonella Infections, Animal</term>
<term>Signal Transduction</term>
<term>Young Adult</term>
</keywords>
<keywords scheme="MESH" xml:lang="fr"><term>Adulte</term>
<term>Animaux</term>
<term>Cellules RAW 264.7</term>
<term>Femelle</term>
<term>Humains</term>
<term>Jeune adulte</term>
<term>Modèles biologiques</term>
<term>Phosphorylation</term>
<term>Salmonelloses animales</term>
<term>Souris</term>
<term>Souris de lignée C57BL</term>
<term>Transduction du signal</term>
</keywords>
</textClass>
</profileDesc>
</teiHeader>
<front><div type="abstract" xml:lang="en">The dynamic interplay between metabolism and immune responses in health and disease, by which different immune cells impact on metabolic processes, are being increasingly appreciated. However, the potential of master regulators of metabolism to control innate immunity are less understood. Here, we studied the cross-talk between leptin signaling and macrophage function in the context of bacterial infections. We found that upon infection with Gram-negative pathogens, such as <i>Salmonella</i>
 Typhimurium, leptin receptor (Lepr) expression increased in both mouse and human macrophages. Unexpectedly, both genetic <i>Lepr</i>
 ablation in macrophages and global pharmacologic leptin antagonization augmented lysosomal functions, reduced <i>S</i>
 Typhimurium burden, and diminished inflammation in vitro and in vivo. Mechanistically, we show that leptin induction activates the mTORC2/Akt pathway and subsequently down-regulates Phlpp1 phosphatase, allowing for phosphorylated Akt to impair lysosomal-mediated pathogen clearance. These data highlight a link between leptin signaling, the mTORC2/Phlpp1/Akt axis, and lysosomal activity in macrophages and have important therapeutic implications for modulating innate immunity to combat Gram-negative bacterial infections.</div>
</front>
</TEI>
<pubmed><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">31350351</PMID>
<DateCompleted><Year>2020</Year>
<Month>03</Month>
<Day>25</Day>
</DateCompleted>
<DateRevised><Year>2020</Year>
<Month>03</Month>
<Day>25</Day>
</DateRevised>
<Article PubModel="Print-Electronic"><Journal><ISSN IssnType="Electronic">1091-6490</ISSN>
<JournalIssue CitedMedium="Internet"><Volume>116</Volume>
<Issue>33</Issue>
<PubDate><Year>2019</Year>
<Month>08</Month>
<Day>13</Day>
</PubDate>
</JournalIssue>
<Title>Proceedings of the National Academy of Sciences of the United States of America</Title>
<ISOAbbreviation>Proc Natl Acad Sci U S A</ISOAbbreviation>
</Journal>
<ArticleTitle>Leptin signaling impairs macrophage defenses against <i>Salmonella</i>
 Typhimurium.</ArticleTitle>
<Pagination><MedlinePgn>16551-16560</MedlinePgn>
</Pagination>
<ELocationID EIdType="doi" ValidYN="Y">10.1073/pnas.1904885116</ELocationID>
<Abstract><AbstractText>The dynamic interplay between metabolism and immune responses in health and disease, by which different immune cells impact on metabolic processes, are being increasingly appreciated. However, the potential of master regulators of metabolism to control innate immunity are less understood. Here, we studied the cross-talk between leptin signaling and macrophage function in the context of bacterial infections. We found that upon infection with Gram-negative pathogens, such as <i>Salmonella</i>
 Typhimurium, leptin receptor (Lepr) expression increased in both mouse and human macrophages. Unexpectedly, both genetic <i>Lepr</i>
 ablation in macrophages and global pharmacologic leptin antagonization augmented lysosomal functions, reduced <i>S</i>
 Typhimurium burden, and diminished inflammation in vitro and in vivo. Mechanistically, we show that leptin induction activates the mTORC2/Akt pathway and subsequently down-regulates Phlpp1 phosphatase, allowing for phosphorylated Akt to impair lysosomal-mediated pathogen clearance. These data highlight a link between leptin signaling, the mTORC2/Phlpp1/Akt axis, and lysosomal activity in macrophages and have important therapeutic implications for modulating innate immunity to combat Gram-negative bacterial infections.</AbstractText>
<CopyrightInformation>Copyright © 2019 the Author(s). Published by PNAS.</CopyrightInformation>
</Abstract>
<AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Fischer</LastName>
<ForeName>Julia</ForeName>
<Initials>J</Initials>
<AffiliationInfo><Affiliation>Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, 50931 Cologne, Germany.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>Department I of Internal Medicine, University of Cologne, D-50937 Cologne, Germany.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>Division of Infectious Diseases, University of Cologne, D-50937 Cologne, Germany.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>Partner Site Bonn-Cologne, German Center for Infection Research (DZIF), D-50931 Cologne, Germany.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>Center for Molecular Medicine Cologne, University of Cologne, 50931 Cologne, Germany.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Gutièrrez</LastName>
<ForeName>Saray</ForeName>
<Initials>S</Initials>
<AffiliationInfo><Affiliation>Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, 50931 Cologne, Germany.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>Institute for Medical Microbiology, Immunology and Hygiene, University of Cologne, 50935 Cologne, Germany.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Ganesan</LastName>
<ForeName>Raja</ForeName>
<Initials>R</Initials>
<AffiliationInfo><Affiliation>Center for Cancer Biology, University of South Australia and SA Pathology, Adelaide SA 5001, Australia.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Calabrese</LastName>
<ForeName>Chiara</ForeName>
<Initials>C</Initials>
<AffiliationInfo><Affiliation>Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, 50931 Cologne, Germany.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Ranjan</LastName>
<ForeName>Rajeev</ForeName>
<Initials>R</Initials>
<AffiliationInfo><Affiliation>Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, 50931 Cologne, Germany.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Cildir</LastName>
<ForeName>Gökhan</ForeName>
<Initials>G</Initials>
<AffiliationInfo><Affiliation>Center for Cancer Biology, University of South Australia and SA Pathology, Adelaide SA 5001, Australia.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Hos</LastName>
<ForeName>Nina Judith</ForeName>
<Initials>NJ</Initials>
<AffiliationInfo><Affiliation>Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, 50931 Cologne, Germany.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>Partner Site Bonn-Cologne, German Center for Infection Research (DZIF), D-50931 Cologne, Germany.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>Institute for Medical Microbiology, Immunology and Hygiene, University of Cologne, 50935 Cologne, Germany.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Rybniker</LastName>
<ForeName>Jan</ForeName>
<Initials>J</Initials>
<AffiliationInfo><Affiliation>Department I of Internal Medicine, University of Cologne, D-50937 Cologne, Germany.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>Division of Infectious Diseases, University of Cologne, D-50937 Cologne, Germany.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>Partner Site Bonn-Cologne, German Center for Infection Research (DZIF), D-50931 Cologne, Germany.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>Center for Molecular Medicine Cologne, University of Cologne, 50931 Cologne, Germany.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>Institute for Medical Microbiology, Immunology and Hygiene, University of Cologne, 50935 Cologne, Germany.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Wolke</LastName>
<ForeName>Martina</ForeName>
<Initials>M</Initials>
<AffiliationInfo><Affiliation>Institute for Medical Microbiology, Immunology and Hygiene, University of Cologne, 50935 Cologne, Germany.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Fries</LastName>
<ForeName>Jochen W U</ForeName>
<Initials>JWU</Initials>
<AffiliationInfo><Affiliation>Institute of Pathology, University of Cologne, D-50931 Cologne, Germany.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Tergaonkar</LastName>
<ForeName>Vinay</ForeName>
<Initials>V</Initials>
<AffiliationInfo><Affiliation>Center for Cancer Biology, University of South Australia and SA Pathology, Adelaide SA 5001, Australia.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>Laboratory of NF-κB Signaling, Institute of Molecular and Cell Biology, Proteos, 138673 Singapore, Singapore.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>Department of Biochemistry, National University of Singapore (NUS), 117597 Singapore.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>Department of Pathology, Yong Loo Lin School of Medicine, NUS, 117597 Singapore.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Plum</LastName>
<ForeName>Georg</ForeName>
<Initials>G</Initials>
<AffiliationInfo><Affiliation>Institute for Medical Microbiology, Immunology and Hygiene, University of Cologne, 50935 Cologne, Germany.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Antebi</LastName>
<ForeName>Adam</ForeName>
<Initials>A</Initials>
<Identifier Source="ORCID">0000-0002-7241-3029</Identifier>
<AffiliationInfo><Affiliation>Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, 50931 Cologne, Germany.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>Molecular Genetics of Ageing Laboratory, Max Planck Institute for Biology of Ageing, 50931 Cologne, Germany.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Robinson</LastName>
<ForeName>Nirmal</ForeName>
<Initials>N</Initials>
<Identifier Source="ORCID">0000-0002-7361-9491</Identifier>
<AffiliationInfo><Affiliation>Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, 50931 Cologne, Germany; nirmal.robinson@unisa.edu.au.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>Institute for Medical Microbiology, Immunology and Hygiene, University of Cologne, 50935 Cologne, Germany.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>Center for Cancer Biology, University of South Australia and SA Pathology, Adelaide SA 5001, Australia.</Affiliation>
</AffiliationInfo>
</Author>
</AuthorList>
<Language>eng</Language>
<GrantList CompleteYN="Y"><Grant><GrantID>P30 DK026687</GrantID>
<Acronym>DK</Acronym>
<Agency>NIDDK NIH HHS</Agency>
<Country>United States</Country>
</Grant>
</GrantList>
<PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType>
<PublicationType UI="D052061">Research Support, N.I.H., Extramural</PublicationType>
<PublicationType UI="D013485">Research Support, Non-U.S. Gov't</PublicationType>
</PublicationTypeList>
<ArticleDate DateType="Electronic"><Year>2019</Year>
<Month>07</Month>
<Day>26</Day>
</ArticleDate>
</Article>
<MedlineJournalInfo><Country>United States</Country>
<MedlineTA>Proc Natl Acad Sci U S A</MedlineTA>
<NlmUniqueID>7505876</NlmUniqueID>
<ISSNLinking>0027-8424</ISSNLinking>
</MedlineJournalInfo>
<ChemicalList><Chemical><RegistryNumber>0</RegistryNumber>
<NameOfSubstance UI="D020738">Leptin</NameOfSubstance>
</Chemical>
<Chemical><RegistryNumber>0</RegistryNumber>
<NameOfSubstance UI="D054411">Receptors, Leptin</NameOfSubstance>
</Chemical>
<Chemical><RegistryNumber>EC 2.7.11.1</RegistryNumber>
<NameOfSubstance UI="D000076225">Mechanistic Target of Rapamycin Complex 2</NameOfSubstance>
</Chemical>
<Chemical><RegistryNumber>EC 2.7.11.1</RegistryNumber>
<NameOfSubstance UI="D051057">Proto-Oncogene Proteins c-akt</NameOfSubstance>
</Chemical>
<Chemical><RegistryNumber>EC 3.1.3.16</RegistryNumber>
<NameOfSubstance UI="C519282">PHLPP1 protein, mouse</NameOfSubstance>
</Chemical>
<Chemical><RegistryNumber>EC 3.1.3.16</RegistryNumber>
<NameOfSubstance UI="D010749">Phosphoprotein Phosphatases</NameOfSubstance>
</Chemical>
</ChemicalList>
<CitationSubset>IM</CitationSubset>
<MeshHeadingList><MeshHeading><DescriptorName UI="D000328" MajorTopicYN="N">Adult</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D000818" MajorTopicYN="N">Animals</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D005260" MajorTopicYN="N">Female</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D006801" MajorTopicYN="N">Humans</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D007249" MajorTopicYN="N">Inflammation</DescriptorName>
<QualifierName UI="Q000473" MajorTopicYN="N">pathology</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D020738" MajorTopicYN="N">Leptin</DescriptorName>
<QualifierName UI="Q000037" MajorTopicYN="N">antagonists & inhibitors</QualifierName>
<QualifierName UI="Q000378" MajorTopicYN="Y">metabolism</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D008247" MajorTopicYN="N">Lysosomes</DescriptorName>
<QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D008264" MajorTopicYN="N">Macrophages</DescriptorName>
<QualifierName UI="Q000276" MajorTopicYN="Y">immunology</QualifierName>
<QualifierName UI="Q000382" MajorTopicYN="N">microbiology</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D000076225" MajorTopicYN="N">Mechanistic Target of Rapamycin Complex 2</DescriptorName>
<QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D051379" MajorTopicYN="N">Mice</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D008810" MajorTopicYN="N">Mice, Inbred C57BL</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D008954" MajorTopicYN="N">Models, Biological</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D010588" MajorTopicYN="N">Phagosomes</DescriptorName>
<QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D010749" MajorTopicYN="N">Phosphoprotein Phosphatases</DescriptorName>
<QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D010766" MajorTopicYN="N">Phosphorylation</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D051057" MajorTopicYN="N">Proto-Oncogene Proteins c-akt</DescriptorName>
<QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D000067996" MajorTopicYN="N">RAW 264.7 Cells</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D054411" MajorTopicYN="N">Receptors, Leptin</DescriptorName>
<QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D012481" MajorTopicYN="N">Salmonella Infections, Animal</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D012486" MajorTopicYN="N">Salmonella typhimurium</DescriptorName>
<QualifierName UI="Q000276" MajorTopicYN="Y">immunology</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D015398" MajorTopicYN="Y">Signal Transduction</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D055815" MajorTopicYN="N">Young Adult</DescriptorName>
</MeshHeading>
</MeshHeadingList>
<KeywordList Owner="NOTNLM"><Keyword MajorTopicYN="Y">AKT</Keyword>
<Keyword MajorTopicYN="Y">Salmonella</Keyword>
<Keyword MajorTopicYN="Y">leptin</Keyword>
<Keyword MajorTopicYN="Y">lysosomes</Keyword>
<Keyword MajorTopicYN="Y">macrophages</Keyword>
</KeywordList>
<CoiStatement>The authors declare no conflict of interest.</CoiStatement>
</MedlineCitation>
<PubmedData><History><PubMedPubDate PubStatus="pubmed"><Year>2019</Year>
<Month>7</Month>
<Day>28</Day>
<Hour>6</Hour>
<Minute>0</Minute>
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<PublicationStatus>ppublish</PublicationStatus>
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<ArticleId IdType="doi">10.1073/pnas.1904885116</ArticleId>
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<affiliations><list><country><li>Allemagne</li>
<li>Australie</li>
<li>Singapour</li>
</country>
<region><li>District de Cologne</li>
<li>Rhénanie-du-Nord-Westphalie</li>
</region>
<settlement><li>Cologne</li>
</settlement>
<orgName><li>Université nationale de Singapour</li>
</orgName>
</list>
<tree><country name="Allemagne"><region name="Rhénanie-du-Nord-Westphalie"><name sortKey="Fischer, Julia" sort="Fischer, Julia" uniqKey="Fischer J" first="Julia" last="Fischer">Julia Fischer</name>
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<name sortKey="Antebi, Adam" sort="Antebi, Adam" uniqKey="Antebi A" first="Adam" last="Antebi">Adam Antebi</name>
<name sortKey="Antebi, Adam" sort="Antebi, Adam" uniqKey="Antebi A" first="Adam" last="Antebi">Adam Antebi</name>
<name sortKey="Calabrese, Chiara" sort="Calabrese, Chiara" uniqKey="Calabrese C" first="Chiara" last="Calabrese">Chiara Calabrese</name>
<name sortKey="Fischer, Julia" sort="Fischer, Julia" uniqKey="Fischer J" first="Julia" last="Fischer">Julia Fischer</name>
<name sortKey="Fischer, Julia" sort="Fischer, Julia" uniqKey="Fischer J" first="Julia" last="Fischer">Julia Fischer</name>
<name sortKey="Fischer, Julia" sort="Fischer, Julia" uniqKey="Fischer J" first="Julia" last="Fischer">Julia Fischer</name>
<name sortKey="Fischer, Julia" sort="Fischer, Julia" uniqKey="Fischer J" first="Julia" last="Fischer">Julia Fischer</name>
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<name sortKey="Hos, Nina Judith" sort="Hos, Nina Judith" uniqKey="Hos N" first="Nina Judith" last="Hos">Nina Judith Hos</name>
<name sortKey="Hos, Nina Judith" sort="Hos, Nina Judith" uniqKey="Hos N" first="Nina Judith" last="Hos">Nina Judith Hos</name>
<name sortKey="Plum, Georg" sort="Plum, Georg" uniqKey="Plum G" first="Georg" last="Plum">Georg Plum</name>
<name sortKey="Ranjan, Rajeev" sort="Ranjan, Rajeev" uniqKey="Ranjan R" first="Rajeev" last="Ranjan">Rajeev Ranjan</name>
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<name sortKey="Rybniker, Jan" sort="Rybniker, Jan" uniqKey="Rybniker J" first="Jan" last="Rybniker">Jan Rybniker</name>
<name sortKey="Rybniker, Jan" sort="Rybniker, Jan" uniqKey="Rybniker J" first="Jan" last="Rybniker">Jan Rybniker</name>
<name sortKey="Rybniker, Jan" sort="Rybniker, Jan" uniqKey="Rybniker J" first="Jan" last="Rybniker">Jan Rybniker</name>
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<name sortKey="Cildir, Gokhan" sort="Cildir, Gokhan" uniqKey="Cildir G" first="Gökhan" last="Cildir">Gökhan Cildir</name>
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<name sortKey="Robinson, Nirmal" sort="Robinson, Nirmal" uniqKey="Robinson N" first="Nirmal" last="Robinson">Nirmal Robinson</name>
<name sortKey="Tergaonkar, Vinay" sort="Tergaonkar, Vinay" uniqKey="Tergaonkar V" first="Vinay" last="Tergaonkar">Vinay Tergaonkar</name>
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<country name="Singapour"><noRegion><name sortKey="Tergaonkar, Vinay" sort="Tergaonkar, Vinay" uniqKey="Tergaonkar V" first="Vinay" last="Tergaonkar">Vinay Tergaonkar</name>
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{{Explor lien
   |wiki=    Bois
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   |type=    RBID
   |clé=     pubmed:31350351
   |texte=   Leptin signaling impairs macrophage defenses against Salmonella Typhimurium.
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	Serveur d'exploration sur la rapamycine et les champignons
	Attention, ce site est en cours de développement ! Attention, site généré par des moyens informatiques à partir de corpus bruts. Les informations ne sont donc pas validées.

Serveur d'exploration sur la rapamycine et les champignons

Leptin signaling impairs macrophage defenses against Salmonella Typhimurium.

Leptin signaling impairs macrophage defenses against Salmonella Typhimurium.

Source :

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Abstract

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