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© A. Alanio, E. Perret
Prolifération de Cryptococcus neoformans dans des macrophages murins.
Publication : Nature communications

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

Scientific Fields
Diseases
Organisms
Applications
Technique

Published in Nature communications - 08 May 2020

Gonçalves SM, Duarte-Oliveira C, Campos CF, Aimanianda V, Ter Horst R, Leite L, Mercier T, Pereira P, Fernández-García M, Antunes D, Rodrigues CS, Barbosa-Matos C, Gaifem J, Mesquita I, Marques A, Osório NS, Torrado E, Rodrigues F, Costa S, Joosten LA, Lagrou K, Maertens J, Lacerda JF, Campos A, Brown GD, Brakhage AA, Barbas C, Silvestre R, van de Veerdonk FL, Chamilos G, Netea MG, Latgé JP, Cunha C, Carvalho A,

Link to Pubmed [PMID] – 32385235

Link to DOI [DOI] – 10.1038/s41467-020-16120-z

2020 05; 11(1): 2282

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.

https://pubmed.ncbi.nlm.nih.gov/32385235