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

Samuel M. Gonçalves, Cláudio Duarte-Oliveira, Cláudia F. Campos, Vishukumar Aimanianda, Rob Horst, Luis Leite, Toine Mercier, Paulo Pereira, Miguel Fernández-García, Daniela Antunes, Cláudia S. Rodrigues, Catarina Barbosa-Matos, Joana Gaifem, Inês Mesquita, António Marques, Nuno S. Osório, Egídio Torrado, Fernando Rodrigues, Sandra Costa, Leo AB. Joosten, Katrien Lagrou, Johan Maertens, João F. Lacerda, António Campos, Gordon D. Brown, Axel A. Brakhage, Coral Barbas, Ricardo Silvestre, Frank L. Veerdonk, Georgios Chamilos, Mihai G. Netea, Jean-Paul Latgé, Cristina Cunha and Agostinho Carvalho ()
Additional contact information
Samuel M. Gonçalves: University of Minho
Cláudio Duarte-Oliveira: University of Minho
Cláudia F. Campos: University of Minho
Vishukumar Aimanianda: Institut Pasteur
Rob Horst: Radboud University Medical Centre
Luis Leite: Instituto Português de Oncologia
Toine Mercier: UZ Leuven
Paulo Pereira: Faculdade de Medicina de Lisboa
Miguel Fernández-García: Faculty of Pharmacy, San Pablo CEU University
Daniela Antunes: University of Minho
Cláudia S. Rodrigues: University of Minho
Catarina Barbosa-Matos: University of Minho
Joana Gaifem: University of Minho
Inês Mesquita: University of Minho
António Marques: Hospital de Braga
Nuno S. Osório: University of Minho
Egídio Torrado: University of Minho
Fernando Rodrigues: University of Minho
Sandra Costa: University of Minho
Leo AB. Joosten: Radboud University Medical Centre
Katrien Lagrou: KU Leuven
Johan Maertens: UZ Leuven
João F. Lacerda: Faculdade de Medicina de Lisboa
António Campos: Instituto Português de Oncologia
Gordon D. Brown: University of Aberdeen
Axel A. Brakhage: Leibniz-Institute for Natural Product Research and Infection Biology
Coral Barbas: Faculty of Pharmacy, San Pablo CEU University
Ricardo Silvestre: University of Minho
Frank L. Veerdonk: Radboud University Medical Centre
Georgios Chamilos: University of Crete
Mihai G. Netea: Radboud University Medical Centre
Jean-Paul Latgé: Institut Pasteur
Cristina Cunha: University of Minho
Agostinho Carvalho: University of Minho

Nature Communications, 2020, vol. 11, issue 1, 1-15

Abstract: 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.

Date: 2020
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-020-16120-z Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-16120-z

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-020-16120-z

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().