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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
general
Phagosomal removal of fungal melanin reprograms macrophage metabolism to promote antifungal immunity
Nature Communications, Volume 11, No. 1, Article 2282, Year 2020
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Description
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. © 2020, The Author(s).
Authors & Co-Authors
Aimanianda, Vishukumar
France, Paris
Institut Pasteur, Paris
Fernández-García, Miguel
Spain, Madrid
Universidad Ceu San Pablo
Osório, Nuno S.
Portugal, Braga
Universidade do Minho
Torrado, Egídio
Portugal, Braga
Universidade do Minho
Rodrigues, Fernando José Santos
Portugal, Braga
Universidade do Minho
Joosten, Leo A.B.
Netherlands, Nijmegen
Radboud University Medical Center
Lagrou, Katrien
Belgium, Leuven
Ku Leuven
Belgium, Leuven
Ku Leuven– University Hospital Leuven
Maertens, Johan A.
Belgium, Leuven
Ku Leuven– University Hospital Leuven
Belgium, Leuven
Ku Leuven
Campos, António M.
Portugal, Porto
Instituto Português de Oncologia do Porto fg
Brown, Gordon D.A.
United Kingdom, Aberdeen
University of Aberdeen
Brakhage, Axel A.
Germany, Jena
Leibniz-institut Für Naturstoff-forschung Und Infektionsbiologie E. V. – Hans-knöll-institut
Germany, Jena
Friedrich-schiller-universität Jena
Barbas, Coral
Spain, Madrid
Universidad Ceu San Pablo
Silvestre, R. J.
Portugal, Braga
Universidade do Minho
van de Veerdonk, Frank Leo
Netherlands, Nijmegen
Radboud University Medical Center
Chamilos, Georgios
Greece, Rethymnon
University of Crete
Greece, Heraklion
Foundation for Research and Technology-hellas
Netea, Mihai Gheorghe
Netherlands, Nijmegen
Radboud University Medical Center
Germany, Bonn
Universität Bonn
Latgé, Jean Paul
France, Paris
Institut Pasteur, Paris
Cunha, Cristina A.
Portugal, Braga
Universidade do Minho
Carvalho, Agostinho
Portugal, Braga
Universidade do Minho
Statistics
Citations: 58
Authors: 19
Affiliations: 15
Identifiers
Doi:
10.1038/s41467-020-16120-z
ISSN:
20411723
Research Areas
Genetics And Genomics
Noncommunicable Diseases