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

Author

Listed:
  • Samuel M. Gonçalves

    (University of Minho
    ICVS/3B’s - PT Government Associate Laboratory)

  • Cláudio Duarte-Oliveira

    (University of Minho
    ICVS/3B’s - PT Government Associate Laboratory)

  • Cláudia F. Campos

    (University of Minho
    ICVS/3B’s - PT Government Associate Laboratory)

  • Vishukumar Aimanianda

    (Institut Pasteur)

  • Rob Horst

    (Radboud University Medical Centre)

  • Luis Leite

    (Instituto Português de Oncologia)

  • Toine Mercier

    (UZ Leuven
    KU Leuven)

  • Paulo Pereira

    (Faculdade de Medicina de Lisboa)

  • Miguel Fernández-García

    (Faculty of Pharmacy, San Pablo CEU University)

  • Daniela Antunes

    (University of Minho
    ICVS/3B’s - PT Government Associate Laboratory)

  • Cláudia S. Rodrigues

    (University of Minho
    ICVS/3B’s - PT Government Associate Laboratory)

  • Catarina Barbosa-Matos

    (University of Minho
    ICVS/3B’s - PT Government Associate Laboratory)

  • Joana Gaifem

    (University of Minho
    ICVS/3B’s - PT Government Associate Laboratory)

  • Inês Mesquita

    (University of Minho
    ICVS/3B’s - PT Government Associate Laboratory)

  • António Marques

    (Hospital de Braga)

  • Nuno S. Osório

    (University of Minho
    ICVS/3B’s - PT Government Associate Laboratory)

  • Egídio Torrado

    (University of Minho
    ICVS/3B’s - PT Government Associate Laboratory)

  • Fernando Rodrigues

    (University of Minho
    ICVS/3B’s - PT Government Associate Laboratory)

  • Sandra Costa

    (University of Minho
    ICVS/3B’s - PT Government Associate Laboratory)

  • Leo AB. Joosten

    (Radboud University Medical Centre)

  • Katrien Lagrou

    (KU Leuven
    UZ Leuven)

  • Johan Maertens

    (UZ Leuven
    KU 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
    Friedrich Schiller University)

  • Coral Barbas

    (Faculty of Pharmacy, San Pablo CEU University)

  • Ricardo Silvestre

    (University of Minho
    ICVS/3B’s - PT Government Associate Laboratory)

  • Frank L. Veerdonk

    (Radboud University Medical Centre)

  • Georgios Chamilos

    (University of Crete
    FORTH)

  • Mihai G. Netea

    (Radboud University Medical Centre
    University of Bonn)

  • Jean-Paul Latgé

    (Institut Pasteur)

  • Cristina Cunha

    (University of Minho
    ICVS/3B’s - PT Government Associate Laboratory)

  • Agostinho Carvalho

    (University of Minho
    ICVS/3B’s - PT Government Associate Laboratory)

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.

Suggested Citation

  • 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, 2020. "Phagosomal removal of fungal melanin reprograms macrophage metabolism to promote antifungal immunity," Nature Communications, Nature, vol. 11(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-16120-z
    DOI: 10.1038/s41467-020-16120-z
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