RapamycinFungusV1, Main, Exploration, bibRecord, 000072

Phagosomal removal of fungal melanin reprograms macrophage metabolism to promote antifungal immunity.

Identifieur interne : 000072 ( Main/Exploration ); précédent : 000071; suivant : 000073

Phagosomal removal of fungal melanin reprograms macrophage metabolism to promote antifungal immunity.

Auteurs : Samuel M. Gonçalves [Portugal] ; Cláudio Duarte-Oliveira [Portugal] ; Cláudia F. Campos [Portugal] ; Vishukumar Aimanianda [France] ; Rob Ter Horst [Pays-Bas] ; Luis Leite [Portugal] ; Toine Mercier [Belgique] ; Paulo Pereira [Portugal] ; Miguel Fernández-García [Espagne] ; Daniela Antunes [Portugal] ; Cláudia S. Rodrigues [Portugal] ; Catarina Barbosa-Matos [Portugal] ; Joana Gaifem [Portugal] ; Inês Mesquita [Portugal] ; Ant Nio Marques [Portugal] ; Nuno S. Os Rio [Portugal] ; Egídio Torrado [Portugal] ; Fernando Rodrigues [Portugal] ; Sandra Costa [Portugal] ; Leo Ab Joosten [Pays-Bas] ; Katrien Lagrou [Belgique] ; Johan Maertens [Belgique] ; João F. Lacerda [Portugal] ; Ant Nio Campos [Portugal] ; Gordon D. Brown [Royaume-Uni] ; Axel A. Brakhage [Allemagne] ; Coral Barbas [Espagne] ; Ricardo Silvestre [Portugal] ; Frank L. Van De Veerdonk [Pays-Bas] ; Georgios Chamilos [Grèce] ; Mihai G. Netea [Pays-Bas, Allemagne] ; Jean-Paul Latgé [France] ; Cristina Cunha [Portugal] ; Agostinho Carvalho [Portugal]

Source :

Nature communications [ 2041-1723 ] ; 2020.

RBID : pubmed:32385235

Descripteurs français

KwdFr :
- Animaux (MeSH), Aspergillus fumigatus (immunologie), Glucose (métabolisme), Glycolyse (MeSH), Humains (MeSH), Immunité (MeSH), Lactates (métabolisme), Macrophages (immunologie), Macrophages (microbiologie), Mélanines (métabolisme), Phagosomes (métabolisme), Signalisation calcique (MeSH), Souris de lignée C57BL (MeSH), Sous-unité alpha du facteur-1 induit par l'hypoxie (métabolisme), Sérine-thréonine kinases TOR (métabolisme), Transcriptome (génétique).
MESH :
- génétique : Transcriptome.
- immunologie : Aspergillus fumigatus, Macrophages.
- microbiologie : Macrophages.
- métabolisme : Glucose, Lactates, Mélanines, Phagosomes, Sous-unité alpha du facteur-1 induit par l'hypoxie, Sérine-thréonine kinases TOR.
- Animaux, Glycolyse, Humains, Immunité, Signalisation calcique, Souris de lignée C57BL.

English descriptors

KwdEn :
- Animals (MeSH), Aspergillus fumigatus (immunology), Calcium Signaling (MeSH), Glucose (metabolism), Glycolysis (MeSH), Humans (MeSH), Hypoxia-Inducible Factor 1, alpha Subunit (metabolism), Immunity (MeSH), Lactates (metabolism), Macrophages (immunology), Macrophages (microbiology), Melanins (metabolism), Mice, Inbred C57BL (MeSH), Phagosomes (metabolism), TOR Serine-Threonine Kinases (metabolism), Transcriptome (genetics).
MESH :
- chemical , metabolism : Glucose, Hypoxia-Inducible Factor 1, alpha Subunit, Lactates, Melanins, TOR Serine-Threonine Kinases.
- genetics : Transcriptome.
- immunology : Aspergillus fumigatus, Macrophages.
- metabolism : Phagosomes.
- microbiology : Macrophages.
- Animals, Calcium Signaling, Glycolysis, Humans, Immunity, Mice, Inbred C57BL.

Abstract

In response to infection, macrophages adapt their metabolism rapidly to enhance glycolysis and fuel specialized antimicrobial effector functions. Here we show that fungal melanin is an essential molecule required for the metabolic rewiring of macrophages during infection with the fungal pathogen Aspergillus fumigatus. Using pharmacological and genetic tools, we reveal a molecular link between calcium sequestration by melanin inside the phagosome and induction of glycolysis required for efficient innate immune responses. By remodeling the intracellular calcium machinery and impairing signaling via calmodulin, melanin drives an immunometabolic signaling axis towards glycolysis with activation of hypoxia-inducible factor 1 subunit alpha (HIF-1α) and phagosomal recruitment of mammalian target of rapamycin (mTOR). These data demonstrate a pivotal mechanism in the immunometabolic regulation of macrophages during fungal infection and highlight the metabolic repurposing of immune cells as a potential therapeutic strategy.

DOI: 10.1038/s41467-020-16120-z
PubMed: 32385235
PubMed Central: PMC7210971

Affiliations:

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

to stream Main, to step Corpus: 000078
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Le document en format XML

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<affiliation wicri:level="1"><nlm:affiliation>Department of Microbiology and Immunology, KU Leuven, 3000, Leuven, Belgium.</nlm:affiliation>
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<affiliation wicri:level="1"><nlm:affiliation>Institute of Microbiology, Friedrich Schiller University, 07743, Jena, Germany.</nlm:affiliation>
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<author><name sortKey="Van De Veerdonk, Frank L" sort="Van De Veerdonk, Frank L" uniqKey="Van De Veerdonk F" first="Frank L" last="Van De Veerdonk">Frank L. Van De Veerdonk</name>
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<country xml:lang="fr">Grèce</country>
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<affiliation wicri:level="1"><nlm:affiliation>Institute of Molecular Biology and Biotechnology, FORTH, 70013, Heraklion, Greece.</nlm:affiliation>
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<affiliation wicri:level="3"><nlm:affiliation>Department of Genomics & Immunoregulation, Life and Medical Sciences Institute, University of Bonn, 53115, Bonn, Germany.</nlm:affiliation>
<country xml:lang="fr">Allemagne</country>
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<author><name sortKey="Latge, Jean Paul" sort="Latge, Jean Paul" uniqKey="Latge J" first="Jean-Paul" last="Latgé">Jean-Paul Latgé</name>
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<sourceDesc><biblStruct><analytic><title xml:lang="en">Phagosomal removal of fungal melanin reprograms macrophage metabolism to promote antifungal immunity.</title>
<author><name sortKey="Goncalves, Samuel M" sort="Goncalves, Samuel M" uniqKey="Goncalves S" first="Samuel M" last="Gonçalves">Samuel M. Gonçalves</name>
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<country xml:lang="fr">Portugal</country>
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<affiliation wicri:level="1"><nlm:affiliation>ICVS/3B's - PT Government Associate Laboratory, Guimarães/Braga, Portugal.</nlm:affiliation>
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<author><name sortKey="Duarte Oliveira, Claudio" sort="Duarte Oliveira, Claudio" uniqKey="Duarte Oliveira C" first="Cláudio" last="Duarte-Oliveira">Cláudio Duarte-Oliveira</name>
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<country xml:lang="fr">Portugal</country>
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<affiliation wicri:level="1"><nlm:affiliation>ICVS/3B's - PT Government Associate Laboratory, Guimarães/Braga, Portugal.</nlm:affiliation>
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<author><name sortKey="Campos, Claudia F" sort="Campos, Claudia F" uniqKey="Campos C" first="Cláudia F" last="Campos">Cláudia F. Campos</name>
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<country xml:lang="fr">Portugal</country>
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<affiliation wicri:level="1"><nlm:affiliation>ICVS/3B's - PT Government Associate Laboratory, Guimarães/Braga, Portugal.</nlm:affiliation>
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<author><name sortKey="Aimanianda, Vishukumar" sort="Aimanianda, Vishukumar" uniqKey="Aimanianda V" first="Vishukumar" last="Aimanianda">Vishukumar Aimanianda</name>
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<author><name sortKey="Ter Horst, Rob" sort="Ter Horst, Rob" uniqKey="Ter Horst R" first="Rob" last="Ter Horst">Rob Ter Horst</name>
<affiliation wicri:level="3"><nlm:affiliation>Department of Internal Medicine and Radboud Center for Infectious Diseases, Radboud University Medical Centre, 6500HB, Nijmegen, Netherlands.</nlm:affiliation>
<country xml:lang="fr">Pays-Bas</country>
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<author><name sortKey="Leite, Luis" sort="Leite, Luis" uniqKey="Leite L" first="Luis" last="Leite">Luis Leite</name>
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<author><name sortKey="Mercier, Toine" sort="Mercier, Toine" uniqKey="Mercier T" first="Toine" last="Mercier">Toine Mercier</name>
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<country xml:lang="fr">Belgique</country>
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<affiliation wicri:level="1"><nlm:affiliation>Department of Microbiology and Immunology, KU Leuven, 3000, Leuven, Belgium.</nlm:affiliation>
<country xml:lang="fr">Belgique</country>
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<author><name sortKey="Pereira, Paulo" sort="Pereira, Paulo" uniqKey="Pereira P" first="Paulo" last="Pereira">Paulo Pereira</name>
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<author><name sortKey="Fernandez Garcia, Miguel" sort="Fernandez Garcia, Miguel" uniqKey="Fernandez Garcia M" first="Miguel" last="Fernández-García">Miguel Fernández-García</name>
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<country xml:lang="fr">Espagne</country>
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<author><name sortKey="Antunes, Daniela" sort="Antunes, Daniela" uniqKey="Antunes D" first="Daniela" last="Antunes">Daniela Antunes</name>
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<country xml:lang="fr">Portugal</country>
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<affiliation wicri:level="1"><nlm:affiliation>ICVS/3B's - PT Government Associate Laboratory, Guimarães/Braga, Portugal.</nlm:affiliation>
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<author><name sortKey="Rodrigues, Claudia S" sort="Rodrigues, Claudia S" uniqKey="Rodrigues C" first="Cláudia S" last="Rodrigues">Cláudia S. Rodrigues</name>
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<country xml:lang="fr">Portugal</country>
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<author><name sortKey="Barbosa Matos, Catarina" sort="Barbosa Matos, Catarina" uniqKey="Barbosa Matos C" first="Catarina" last="Barbosa-Matos">Catarina Barbosa-Matos</name>
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<country xml:lang="fr">Portugal</country>
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<author><name sortKey="Gaifem, Joana" sort="Gaifem, Joana" uniqKey="Gaifem J" first="Joana" last="Gaifem">Joana Gaifem</name>
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<country xml:lang="fr">Portugal</country>
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<author><name sortKey="Mesquita, Ines" sort="Mesquita, Ines" uniqKey="Mesquita I" first="Inês" last="Mesquita">Inês Mesquita</name>
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<affiliation wicri:level="1"><nlm:affiliation>ICVS/3B's - PT Government Associate Laboratory, Guimarães/Braga, Portugal.</nlm:affiliation>
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<author><name sortKey="Marques, Ant Nio" sort="Marques, Ant Nio" uniqKey="Marques A" first="Ant Nio" last="Marques">Ant Nio Marques</name>
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<author><name sortKey="Os Rio, Nuno S" sort="Os Rio, Nuno S" uniqKey="Os Rio N" first="Nuno S" last="Os Rio">Nuno S. Os Rio</name>
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<country xml:lang="fr">Portugal</country>
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<orgName type="university">Université du Minho</orgName>
<placeName><settlement type="city">Braga</settlement>
<region>Région Nord (Portugal)</region>
</placeName>
</affiliation>
<affiliation wicri:level="1"><nlm:affiliation>ICVS/3B's - PT Government Associate Laboratory, Guimarães/Braga, Portugal.</nlm:affiliation>
<country xml:lang="fr">Portugal</country>
<wicri:regionArea>ICVS/3B's - PT Government Associate Laboratory, Guimarães/Braga</wicri:regionArea>
<wicri:noRegion>Guimarães/Braga</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Torrado, Egidio" sort="Torrado, Egidio" uniqKey="Torrado E" first="Egídio" last="Torrado">Egídio Torrado</name>
<affiliation wicri:level="4"><nlm:affiliation>Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, 4710-057, Braga, Portugal.</nlm:affiliation>
<country xml:lang="fr">Portugal</country>
<wicri:regionArea>Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, 4710-057, Braga</wicri:regionArea>
<orgName type="university">Université du Minho</orgName>
<placeName><settlement type="city">Braga</settlement>
<region>Région Nord (Portugal)</region>
</placeName>
</affiliation>
<affiliation wicri:level="1"><nlm:affiliation>ICVS/3B's - PT Government Associate Laboratory, Guimarães/Braga, Portugal.</nlm:affiliation>
<country xml:lang="fr">Portugal</country>
<wicri:regionArea>ICVS/3B's - PT Government Associate Laboratory, Guimarães/Braga</wicri:regionArea>
<wicri:noRegion>Guimarães/Braga</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Rodrigues, Fernando" sort="Rodrigues, Fernando" uniqKey="Rodrigues F" first="Fernando" last="Rodrigues">Fernando Rodrigues</name>
<affiliation wicri:level="4"><nlm:affiliation>Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, 4710-057, Braga, Portugal.</nlm:affiliation>
<country xml:lang="fr">Portugal</country>
<wicri:regionArea>Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, 4710-057, Braga</wicri:regionArea>
<orgName type="university">Université du Minho</orgName>
<placeName><settlement type="city">Braga</settlement>
<region>Région Nord (Portugal)</region>
</placeName>
</affiliation>
<affiliation wicri:level="1"><nlm:affiliation>ICVS/3B's - PT Government Associate Laboratory, Guimarães/Braga, Portugal.</nlm:affiliation>
<country xml:lang="fr">Portugal</country>
<wicri:regionArea>ICVS/3B's - PT Government Associate Laboratory, Guimarães/Braga</wicri:regionArea>
<wicri:noRegion>Guimarães/Braga</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Costa, Sandra" sort="Costa, Sandra" uniqKey="Costa S" first="Sandra" last="Costa">Sandra Costa</name>
<affiliation wicri:level="4"><nlm:affiliation>Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, 4710-057, Braga, Portugal.</nlm:affiliation>
<country xml:lang="fr">Portugal</country>
<wicri:regionArea>Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, 4710-057, Braga</wicri:regionArea>
<orgName type="university">Université du Minho</orgName>
<placeName><settlement type="city">Braga</settlement>
<region>Région Nord (Portugal)</region>
</placeName>
</affiliation>
<affiliation wicri:level="1"><nlm:affiliation>ICVS/3B's - PT Government Associate Laboratory, Guimarães/Braga, Portugal.</nlm:affiliation>
<country xml:lang="fr">Portugal</country>
<wicri:regionArea>ICVS/3B's - PT Government Associate Laboratory, Guimarães/Braga</wicri:regionArea>
<wicri:noRegion>Guimarães/Braga</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Joosten, Leo Ab" sort="Joosten, Leo Ab" uniqKey="Joosten L" first="Leo Ab" last="Joosten">Leo Ab Joosten</name>
<affiliation wicri:level="3"><nlm:affiliation>Department of Internal Medicine and Radboud Center for Infectious Diseases, Radboud University Medical Centre, 6500HB, Nijmegen, Netherlands.</nlm:affiliation>
<country xml:lang="fr">Pays-Bas</country>
<wicri:regionArea>Department of Internal Medicine and Radboud Center for Infectious Diseases, Radboud University Medical Centre, 6500HB, Nijmegen</wicri:regionArea>
<placeName><settlement type="city">Nimègue</settlement>
<region type="province" nuts="2">Gueldre</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Lagrou, Katrien" sort="Lagrou, Katrien" uniqKey="Lagrou K" first="Katrien" last="Lagrou">Katrien Lagrou</name>
<affiliation wicri:level="1"><nlm:affiliation>Department of Microbiology and Immunology, KU Leuven, 3000, Leuven, Belgium.</nlm:affiliation>
<country xml:lang="fr">Belgique</country>
<wicri:regionArea>Department of Microbiology and Immunology, KU Leuven, 3000, Leuven</wicri:regionArea>
<wicri:noRegion>Leuven</wicri:noRegion>
</affiliation>
<affiliation wicri:level="1"><nlm:affiliation>Department of Laboratory Medicine, UZ Leuven, 3000, Leuven, Belgium.</nlm:affiliation>
<country xml:lang="fr">Belgique</country>
<wicri:regionArea>Department of Laboratory Medicine, UZ Leuven, 3000, Leuven</wicri:regionArea>
<wicri:noRegion>Leuven</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Maertens, Johan" sort="Maertens, Johan" uniqKey="Maertens J" first="Johan" last="Maertens">Johan Maertens</name>
<affiliation wicri:level="1"><nlm:affiliation>Department of Hematology, UZ Leuven, 3000, Leuven, Belgium.</nlm:affiliation>
<country xml:lang="fr">Belgique</country>
<wicri:regionArea>Department of Hematology, UZ Leuven, 3000, Leuven</wicri:regionArea>
<wicri:noRegion>Leuven</wicri:noRegion>
</affiliation>
<affiliation wicri:level="1"><nlm:affiliation>Department of Microbiology and Immunology, KU Leuven, 3000, Leuven, Belgium.</nlm:affiliation>
<country xml:lang="fr">Belgique</country>
<wicri:regionArea>Department of Microbiology and Immunology, KU Leuven, 3000, Leuven</wicri:regionArea>
<wicri:noRegion>Leuven</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Lacerda, Joao F" sort="Lacerda, Joao F" uniqKey="Lacerda J" first="João F" last="Lacerda">João F. Lacerda</name>
<affiliation wicri:level="1"><nlm:affiliation>Instituto de Medicina Molecular, Faculdade de Medicina de Lisboa, 1649-028, Lisboa, Portugal.</nlm:affiliation>
<country xml:lang="fr">Portugal</country>
<wicri:regionArea>Instituto de Medicina Molecular, Faculdade de Medicina de Lisboa, 1649-028, Lisboa</wicri:regionArea>
<wicri:noRegion>Lisboa</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Campos, Ant Nio" sort="Campos, Ant Nio" uniqKey="Campos A" first="Ant Nio" last="Campos">Ant Nio Campos</name>
<affiliation wicri:level="1"><nlm:affiliation>STMO, Instituto Português de Oncologia, 4200-072, Porto, Portugal.</nlm:affiliation>
<country xml:lang="fr">Portugal</country>
<wicri:regionArea>STMO, Instituto Português de Oncologia, 4200-072, Porto</wicri:regionArea>
<wicri:noRegion>Porto</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Brown, Gordon D" sort="Brown, Gordon D" uniqKey="Brown G" first="Gordon D" last="Brown">Gordon D. Brown</name>
<affiliation wicri:level="1"><nlm:affiliation>MRC Centre for Medical Mycology, University of Aberdeen, Aberdeen, AB25 2ZD, UK.</nlm:affiliation>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>MRC Centre for Medical Mycology, University of Aberdeen, Aberdeen, AB25 2ZD</wicri:regionArea>
<wicri:noRegion>AB25 2ZD</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Brakhage, Axel A" sort="Brakhage, Axel A" uniqKey="Brakhage A" first="Axel A" last="Brakhage">Axel A. Brakhage</name>
<affiliation wicri:level="1"><nlm:affiliation>Department of Molecular and Applied Microbiology, Leibniz-Institute for Natural Product Research and Infection Biology, 07745, Jena, Germany.</nlm:affiliation>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Department of Molecular and Applied Microbiology, Leibniz-Institute for Natural Product Research and Infection Biology, 07745, Jena</wicri:regionArea>
<wicri:noRegion>07745, Jena</wicri:noRegion>
<wicri:noRegion>07745, Jena</wicri:noRegion>
<wicri:noRegion>Jena</wicri:noRegion>
</affiliation>
<affiliation wicri:level="1"><nlm:affiliation>Institute of Microbiology, Friedrich Schiller University, 07743, Jena, Germany.</nlm:affiliation>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Institute of Microbiology, Friedrich Schiller University, 07743, Jena</wicri:regionArea>
<wicri:noRegion>07743, Jena</wicri:noRegion>
<wicri:noRegion>07743, Jena</wicri:noRegion>
<wicri:noRegion>Jena</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Barbas, Coral" sort="Barbas, Coral" uniqKey="Barbas C" first="Coral" last="Barbas">Coral Barbas</name>
<affiliation wicri:level="3"><nlm:affiliation>Center for Metabolomics and Bioanalysis, Faculty of Pharmacy, San Pablo CEU University, 28668, Madrid, Spain.</nlm:affiliation>
<country xml:lang="fr">Espagne</country>
<wicri:regionArea>Center for Metabolomics and Bioanalysis, Faculty of Pharmacy, San Pablo CEU University, 28668, Madrid</wicri:regionArea>
<placeName><settlement type="city">Madrid</settlement>
<region nuts="2" type="region">Communauté de Madrid</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Silvestre, Ricardo" sort="Silvestre, Ricardo" uniqKey="Silvestre R" first="Ricardo" last="Silvestre">Ricardo Silvestre</name>
<affiliation wicri:level="4"><nlm:affiliation>Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, 4710-057, Braga, Portugal.</nlm:affiliation>
<country xml:lang="fr">Portugal</country>
<wicri:regionArea>Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, 4710-057, Braga</wicri:regionArea>
<orgName type="university">Université du Minho</orgName>
<placeName><settlement type="city">Braga</settlement>
<region>Région Nord (Portugal)</region>
</placeName>
</affiliation>
<affiliation wicri:level="1"><nlm:affiliation>ICVS/3B's - PT Government Associate Laboratory, Guimarães/Braga, Portugal.</nlm:affiliation>
<country xml:lang="fr">Portugal</country>
<wicri:regionArea>ICVS/3B's - PT Government Associate Laboratory, Guimarães/Braga</wicri:regionArea>
<wicri:noRegion>Guimarães/Braga</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Van De Veerdonk, Frank L" sort="Van De Veerdonk, Frank L" uniqKey="Van De Veerdonk F" first="Frank L" last="Van De Veerdonk">Frank L. Van De Veerdonk</name>
<affiliation wicri:level="3"><nlm:affiliation>Department of Internal Medicine and Radboud Center for Infectious Diseases, Radboud University Medical Centre, 6500HB, Nijmegen, Netherlands.</nlm:affiliation>
<country xml:lang="fr">Pays-Bas</country>
<wicri:regionArea>Department of Internal Medicine and Radboud Center for Infectious Diseases, Radboud University Medical Centre, 6500HB, Nijmegen</wicri:regionArea>
<placeName><settlement type="city">Nimègue</settlement>
<region type="province" nuts="2">Gueldre</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Chamilos, Georgios" sort="Chamilos, Georgios" uniqKey="Chamilos G" first="Georgios" last="Chamilos">Georgios Chamilos</name>
<affiliation wicri:level="1"><nlm:affiliation>School of Medicine, University of Crete, 70013, Heraklion, Greece.</nlm:affiliation>
<country xml:lang="fr">Grèce</country>
<wicri:regionArea>School of Medicine, University of Crete, 70013, Heraklion</wicri:regionArea>
<wicri:noRegion>Heraklion</wicri:noRegion>
</affiliation>
<affiliation wicri:level="1"><nlm:affiliation>Institute of Molecular Biology and Biotechnology, FORTH, 70013, Heraklion, Greece.</nlm:affiliation>
<country xml:lang="fr">Grèce</country>
<wicri:regionArea>Institute of Molecular Biology and Biotechnology, FORTH, 70013, Heraklion</wicri:regionArea>
<wicri:noRegion>Heraklion</wicri:noRegion>
</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 and Radboud Center for Infectious Diseases, Radboud University Medical Centre, 6500HB, Nijmegen, Netherlands.</nlm:affiliation>
<country xml:lang="fr">Pays-Bas</country>
<wicri:regionArea>Department of Internal Medicine and Radboud Center for Infectious Diseases, Radboud University Medical Centre, 6500HB, Nijmegen</wicri:regionArea>
<placeName><settlement type="city">Nimègue</settlement>
<region type="province" nuts="2">Gueldre</region>
</placeName>
</affiliation>
<affiliation wicri:level="3"><nlm:affiliation>Department of Genomics & Immunoregulation, Life and Medical Sciences Institute, University of Bonn, 53115, Bonn, Germany.</nlm:affiliation>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Department of Genomics & Immunoregulation, Life and Medical Sciences Institute, University of Bonn, 53115, Bonn</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">Bonn</settlement>
</placeName>
</affiliation>
</author>
<author><name sortKey="Latge, Jean Paul" sort="Latge, Jean Paul" uniqKey="Latge J" first="Jean-Paul" last="Latgé">Jean-Paul Latgé</name>
<affiliation wicri:level="3"><nlm:affiliation>Unité des Aspergillus, Institut Pasteur, 75015, Paris, France.</nlm:affiliation>
<country xml:lang="fr">France</country>
<wicri:regionArea>Unité des Aspergillus, Institut Pasteur, 75015, Paris</wicri:regionArea>
<placeName><region type="region" nuts="2">Île-de-France</region>
<settlement type="city">Paris</settlement>
</placeName>
</affiliation>
</author>
<author><name sortKey="Cunha, Cristina" sort="Cunha, Cristina" uniqKey="Cunha C" first="Cristina" last="Cunha">Cristina Cunha</name>
<affiliation wicri:level="4"><nlm:affiliation>Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, 4710-057, Braga, Portugal.</nlm:affiliation>
<country xml:lang="fr">Portugal</country>
<wicri:regionArea>Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, 4710-057, Braga</wicri:regionArea>
<orgName type="university">Université du Minho</orgName>
<placeName><settlement type="city">Braga</settlement>
<region>Région Nord (Portugal)</region>
</placeName>
</affiliation>
<affiliation wicri:level="1"><nlm:affiliation>ICVS/3B's - PT Government Associate Laboratory, Guimarães/Braga, Portugal.</nlm:affiliation>
<country xml:lang="fr">Portugal</country>
<wicri:regionArea>ICVS/3B's - PT Government Associate Laboratory, Guimarães/Braga</wicri:regionArea>
<wicri:noRegion>Guimarães/Braga</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Carvalho, Agostinho" sort="Carvalho, Agostinho" uniqKey="Carvalho A" first="Agostinho" last="Carvalho">Agostinho Carvalho</name>
<affiliation wicri:level="4"><nlm:affiliation>Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, 4710-057, Braga, Portugal. agostinhocarvalho@med.uminho.pt.</nlm:affiliation>
<country xml:lang="fr">Portugal</country>
<wicri:regionArea>Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, 4710-057, Braga</wicri:regionArea>
<orgName type="university">Université du Minho</orgName>
<placeName><settlement type="city">Braga</settlement>
<region>Région Nord (Portugal)</region>
</placeName>
</affiliation>
<affiliation wicri:level="1"><nlm:affiliation>ICVS/3B's - PT Government Associate Laboratory, Guimarães/Braga, Portugal. agostinhocarvalho@med.uminho.pt.</nlm:affiliation>
<country xml:lang="fr">Portugal</country>
<wicri:regionArea>ICVS/3B's - PT Government Associate Laboratory, Guimarães/Braga</wicri:regionArea>
<wicri:noRegion>Guimarães/Braga</wicri:noRegion>
</affiliation>
</author>
</analytic>
<series><title level="j">Nature communications</title>
<idno type="eISSN">2041-1723</idno>
<imprint><date when="2020" type="published">2020</date>
</imprint>
</series>
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<profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Animals (MeSH)</term>
<term>Aspergillus fumigatus (immunology)</term>
<term>Calcium Signaling (MeSH)</term>
<term>Glucose (metabolism)</term>
<term>Glycolysis (MeSH)</term>
<term>Humans (MeSH)</term>
<term>Hypoxia-Inducible Factor 1, alpha Subunit (metabolism)</term>
<term>Immunity (MeSH)</term>
<term>Lactates (metabolism)</term>
<term>Macrophages (immunology)</term>
<term>Macrophages (microbiology)</term>
<term>Melanins (metabolism)</term>
<term>Mice, Inbred C57BL (MeSH)</term>
<term>Phagosomes (metabolism)</term>
<term>TOR Serine-Threonine Kinases (metabolism)</term>
<term>Transcriptome (genetics)</term>
</keywords>
<keywords scheme="KwdFr" xml:lang="fr"><term>Animaux (MeSH)</term>
<term>Aspergillus fumigatus (immunologie)</term>
<term>Glucose (métabolisme)</term>
<term>Glycolyse (MeSH)</term>
<term>Humains (MeSH)</term>
<term>Immunité (MeSH)</term>
<term>Lactates (métabolisme)</term>
<term>Macrophages (immunologie)</term>
<term>Macrophages (microbiologie)</term>
<term>Mélanines (métabolisme)</term>
<term>Phagosomes (métabolisme)</term>
<term>Signalisation calcique (MeSH)</term>
<term>Souris de lignée C57BL (MeSH)</term>
<term>Sous-unité alpha du facteur-1 induit par l'hypoxie (métabolisme)</term>
<term>Sérine-thréonine kinases TOR (métabolisme)</term>
<term>Transcriptome (génétique)</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Glucose</term>
<term>Hypoxia-Inducible Factor 1, alpha Subunit</term>
<term>Lactates</term>
<term>Melanins</term>
<term>TOR Serine-Threonine Kinases</term>
</keywords>
<keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>Transcriptome</term>
</keywords>
<keywords scheme="MESH" qualifier="génétique" xml:lang="fr"><term>Transcriptome</term>
</keywords>
<keywords scheme="MESH" qualifier="immunologie" xml:lang="fr"><term>Aspergillus fumigatus</term>
<term>Macrophages</term>
</keywords>
<keywords scheme="MESH" qualifier="immunology" xml:lang="en"><term>Aspergillus fumigatus</term>
<term>Macrophages</term>
</keywords>
<keywords scheme="MESH" qualifier="metabolism" xml:lang="en"><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>Glucose</term>
<term>Lactates</term>
<term>Mélanines</term>
<term>Phagosomes</term>
<term>Sous-unité alpha du facteur-1 induit par l'hypoxie</term>
<term>Sérine-thréonine kinases TOR</term>
</keywords>
<keywords scheme="MESH" xml:lang="en"><term>Animals</term>
<term>Calcium Signaling</term>
<term>Glycolysis</term>
<term>Humans</term>
<term>Immunity</term>
<term>Mice, Inbred C57BL</term>
</keywords>
<keywords scheme="MESH" xml:lang="fr"><term>Animaux</term>
<term>Glycolyse</term>
<term>Humains</term>
<term>Immunité</term>
<term>Signalisation calcique</term>
<term>Souris de lignée C57BL</term>
</keywords>
</textClass>
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<front><div type="abstract" xml:lang="en">In response to infection, macrophages adapt their metabolism rapidly to enhance glycolysis and fuel specialized antimicrobial effector functions. Here we show that fungal melanin is an essential molecule required for the metabolic rewiring of macrophages during infection with the fungal pathogen Aspergillus fumigatus. Using pharmacological and genetic tools, we reveal a molecular link between calcium sequestration by melanin inside the phagosome and induction of glycolysis required for efficient innate immune responses. By remodeling the intracellular calcium machinery and impairing signaling via calmodulin, melanin drives an immunometabolic signaling axis towards glycolysis with activation of hypoxia-inducible factor 1 subunit alpha (HIF-1α) and phagosomal recruitment of mammalian target of rapamycin (mTOR). These data demonstrate a pivotal mechanism in the immunometabolic regulation of macrophages during fungal infection and highlight the metabolic repurposing of immune cells as a potential therapeutic strategy.</div>
</front>
</TEI>
<pubmed><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">32385235</PMID>
<DateCompleted><Year>2020</Year>
<Month>08</Month>
<Day>05</Day>
</DateCompleted>
<DateRevised><Year>2020</Year>
<Month>08</Month>
<Day>05</Day>
</DateRevised>
<Article PubModel="Electronic"><Journal><ISSN IssnType="Electronic">2041-1723</ISSN>
<JournalIssue CitedMedium="Internet"><Volume>11</Volume>
<Issue>1</Issue>
<PubDate><Year>2020</Year>
<Month>05</Month>
<Day>08</Day>
</PubDate>
</JournalIssue>
<Title>Nature communications</Title>
<ISOAbbreviation>Nat Commun</ISOAbbreviation>
</Journal>
<ArticleTitle>Phagosomal removal of fungal melanin reprograms macrophage metabolism to promote antifungal immunity.</ArticleTitle>
<Pagination><MedlinePgn>2282</MedlinePgn>
</Pagination>
<ELocationID EIdType="doi" ValidYN="Y">10.1038/s41467-020-16120-z</ELocationID>
<Abstract><AbstractText>In response to infection, macrophages adapt their metabolism rapidly to enhance glycolysis and fuel specialized antimicrobial effector functions. Here we show that fungal melanin is an essential molecule required for the metabolic rewiring of macrophages during infection with the fungal pathogen Aspergillus fumigatus. Using pharmacological and genetic tools, we reveal a molecular link between calcium sequestration by melanin inside the phagosome and induction of glycolysis required for efficient innate immune responses. By remodeling the intracellular calcium machinery and impairing signaling via calmodulin, melanin drives an immunometabolic signaling axis towards glycolysis with activation of hypoxia-inducible factor 1 subunit alpha (HIF-1α) and phagosomal recruitment of mammalian target of rapamycin (mTOR). These data demonstrate a pivotal mechanism in the immunometabolic regulation of macrophages during fungal infection and highlight the metabolic repurposing of immune cells as a potential therapeutic strategy.</AbstractText>
</Abstract>
<AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Gonçalves</LastName>
<ForeName>Samuel M</ForeName>
<Initials>SM</Initials>
<AffiliationInfo><Affiliation>Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, 4710-057, Braga, Portugal.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>ICVS/3B's - PT Government Associate Laboratory, Guimarães/Braga, Portugal.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Duarte-Oliveira</LastName>
<ForeName>Cláudio</ForeName>
<Initials>C</Initials>
<AffiliationInfo><Affiliation>Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, 4710-057, Braga, Portugal.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>ICVS/3B's - PT Government Associate Laboratory, Guimarães/Braga, Portugal.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Campos</LastName>
<ForeName>Cláudia F</ForeName>
<Initials>CF</Initials>
<AffiliationInfo><Affiliation>Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, 4710-057, Braga, Portugal.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>ICVS/3B's - PT Government Associate Laboratory, Guimarães/Braga, Portugal.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Aimanianda</LastName>
<ForeName>Vishukumar</ForeName>
<Initials>V</Initials>
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   |texte=   Phagosomal removal of fungal melanin reprograms macrophage metabolism to promote antifungal immunity.
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	Serveur d'exploration sur la rapamycine et les champignons
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Phagosomal removal of fungal melanin reprograms macrophage metabolism to promote antifungal immunity.

Phagosomal removal of fungal melanin reprograms macrophage metabolism to promote antifungal immunity.

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