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

Research output: Contribution to journalArticleResearchpeer-review

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 hostand 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.

Original languageEnglish
Pages (from-to)988-1006.e7
Number of pages27
JournalCell Metabolism
Volume27
Issue number5
DOIs
Publication statusPublished - 1 May 2018

Keywords

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

Cite this

@article{ea56882c0e284f168b26e5fcaa22f40d,
title = "Glucose Homeostasis Is Important for Immune Cell Viability during Candida Challenge and Host Survival of Systemic Fungal Infection",
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 hostand 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, fungal infection, GAL4, glucose homeostasis, glycolysis, immunometabolism, macrophage, TYE7, Warburg effect",
author = "Tucey, {Timothy M.} and Jiyoti Verma and Harrison, {Paul F.} and Snelgrove, {Sarah L.} and Lo, {Tricia L.} and Scherer, {Allison K.} and Barugahare, {Adele A.} and Powell, {David R.} and Wheeler, {Robert T.} and Hickey, {Michael J.} and Beilharz, {Traude H.} and Thomas Naderer and Ana Traven",
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language = "English",
volume = "27",
pages = "988--1006.e7",
journal = "Cell Metabolism",
issn = "1550-4131",
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}

Glucose Homeostasis Is Important for Immune Cell Viability during Candida Challenge and Host Survival of Systemic Fungal Infection. / Tucey, Timothy M.; Verma, Jiyoti; Harrison, Paul F.; Snelgrove, Sarah L.; Lo, Tricia L.; Scherer, Allison K.; Barugahare, Adele A.; Powell, David R.; Wheeler, Robert T.; Hickey, Michael J.; Beilharz, Traude H.; Naderer, Thomas; Traven, Ana.

In: Cell Metabolism, Vol. 27, No. 5, 01.05.2018, p. 988-1006.e7.

Research output: Contribution to journalArticleResearchpeer-review

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T1 - Glucose Homeostasis Is Important for Immune Cell Viability during Candida Challenge and Host Survival of Systemic Fungal Infection

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AU - Verma, Jiyoti

AU - Harrison, Paul F.

AU - Snelgrove, Sarah L.

AU - Lo, Tricia L.

AU - Scherer, Allison K.

AU - Barugahare, Adele A.

AU - Powell, David R.

AU - Wheeler, Robert T.

AU - Hickey, Michael J.

AU - Beilharz, Traude H.

AU - Naderer, Thomas

AU - Traven, Ana

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