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Cell Metab. 2018 May 1;27(5):988-1006.e7. doi: 10.1016/j.cmet.2018.03.019.

Glucose Homeostasis Is Important for Immune Cell Viability during Candida Challenge and Host Survival of Systemic Fungal Infection.

Author information

1
Infection and Immunity Program and the Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University, Clayton 3800, VIC, Australia.
2
Bioinformatics Platform, Monash University, Clayton 3800, VIC, Australia.
3
Centre for Inflammatory Diseases, Monash University Department of Medicine, Monash Medical Centre, Clayton 3168, VIC, Australia.
4
Department of Molecular & Biomedical Sciences, University of Maine, Orono, ME, USA.
5
Development and Stem Cells Program and the Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University, Clayton 3800, VIC, Australia.
6
Infection and Immunity Program and the Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University, Clayton 3800, VIC, Australia. Electronic address: thomas.naderer@monash.edu.
7
Infection and Immunity Program and the Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University, Clayton 3800, VIC, Australia. Electronic address: ana.traven@monash.edu.

Abstract

To fight infections, macrophages undergo a metabolic shift whereby increased glycolysis fuels antimicrobial inflammation and killing of pathogens. Here we demonstrate that the pathogen Candida albicans turns this metabolic reprogramming into an Achilles' heel for macrophages. During Candida-macrophage interactions intertwined metabolic shifts occur, with concomitant upregulation of glycolysis in both host and pathogen setting up glucose competition. Candida thrives on multiple carbon sources, but infected macrophages are metabolically trapped in glycolysis and depend on glucose for viability: Candida exploits this limitation by depleting glucose, triggering rapid macrophage death. Using pharmacological or genetic means to modulate glucose metabolism of host and/or pathogen, we show that Candida infection perturbs host glucose homeostasis in the murine candidemia model and demonstrate that glucose supplementation improves host outcomes. Our results support the importance of maintaining glucose homeostasis for immune cell survival during Candida challenge and for host survival in systemic infection.

KEYWORDS:

Candida albicans; GAL4; TYE7; Warburg effect; fungal infection; glucose homeostasis; glycolysis; immunometabolism; macrophage

PMID:
29719235
DOI:
10.1016/j.cmet.2018.03.019

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