Rewiring monocyte glucose metabolism via C-type lectin signaling protects against disseminated candidiasis

Jorge Domínguez-Andrés, Rob J.W. Arts, Rob ter Horst, Mark S. Gresnigt, Sanne P. Smeekens, Jacqueline M. Ratter, Ekta Lachmandas, Lily Boutens, Frank L. van de Veerdonk, Leo A.B. Joosten, Richard A. Notebaart, Carlos Ardavín, Mihai G. Netea

Research output: Contribution to journalArticleAcademicpeer-review

12 Citations (Scopus)

Abstract

Monocytes are innate immune cells that play a pivotal role in antifungal immunity, but little is known regarding the cellular metabolic events that regulate their function during infection. Using complementary transcriptomic and immunological studies in human primary monocytes, we show that activation of monocytes by Candida albicans yeast and hyphae was accompanied by metabolic rewiring induced through C-type lectin-signaling pathways. We describe that the innate immune responses against Candida yeast are energy-demanding processes that lead to the mobilization of intracellular metabolite pools and require induction of glucose metabolism, oxidative phosphorylation and glutaminolysis, while responses to hyphae primarily rely on glycolysis. Experimental models of systemic candidiasis models validated a central role for glucose metabolism in anti-Candida immunity, as the impairment of glycolysis led to increased susceptibility in mice. Collectively, these data highlight the importance of understanding the complex network of metabolic responses triggered during infections, and unveil new potential targets for therapeutic approaches against fungal diseases.

LanguageEnglish
Article numbere1006632
Number of pages23
JournalPLoS Pathogens
Volume13
Issue number9
DOIs
Publication statusPublished - 18 Sep 2017

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C-Type Lectins
Candidiasis
Monocytes
Hyphae
Glycolysis
Candida
Glucose
Immunity
Yeasts
Mycoses
Oxidative Phosphorylation
Metabolic Networks and Pathways
Infection
Candida albicans
Innate Immunity
Theoretical Models
Therapeutics

Cite this

Domínguez-Andrés, J., Arts, R. J. W., ter Horst, R., Gresnigt, M. S., Smeekens, S. P., Ratter, J. M., ... Netea, M. G. (2017). Rewiring monocyte glucose metabolism via C-type lectin signaling protects against disseminated candidiasis. PLoS Pathogens, 13(9), [e1006632]. https://doi.org/10.1371/journal.ppat.1006632
Domínguez-Andrés, Jorge ; Arts, Rob J.W. ; ter Horst, Rob ; Gresnigt, Mark S. ; Smeekens, Sanne P. ; Ratter, Jacqueline M. ; Lachmandas, Ekta ; Boutens, Lily ; van de Veerdonk, Frank L. ; Joosten, Leo A.B. ; Notebaart, Richard A. ; Ardavín, Carlos ; Netea, Mihai G. / Rewiring monocyte glucose metabolism via C-type lectin signaling protects against disseminated candidiasis. In: PLoS Pathogens. 2017 ; Vol. 13, No. 9.
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abstract = "Monocytes are innate immune cells that play a pivotal role in antifungal immunity, but little is known regarding the cellular metabolic events that regulate their function during infection. Using complementary transcriptomic and immunological studies in human primary monocytes, we show that activation of monocytes by Candida albicans yeast and hyphae was accompanied by metabolic rewiring induced through C-type lectin-signaling pathways. We describe that the innate immune responses against Candida yeast are energy-demanding processes that lead to the mobilization of intracellular metabolite pools and require induction of glucose metabolism, oxidative phosphorylation and glutaminolysis, while responses to hyphae primarily rely on glycolysis. Experimental models of systemic candidiasis models validated a central role for glucose metabolism in anti-Candida immunity, as the impairment of glycolysis led to increased susceptibility in mice. Collectively, these data highlight the importance of understanding the complex network of metabolic responses triggered during infections, and unveil new potential targets for therapeutic approaches against fungal diseases.",
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Domínguez-Andrés, J, Arts, RJW, ter Horst, R, Gresnigt, MS, Smeekens, SP, Ratter, JM, Lachmandas, E, Boutens, L, van de Veerdonk, FL, Joosten, LAB, Notebaart, RA, Ardavín, C & Netea, MG 2017, 'Rewiring monocyte glucose metabolism via C-type lectin signaling protects against disseminated candidiasis', PLoS Pathogens, vol. 13, no. 9, e1006632. https://doi.org/10.1371/journal.ppat.1006632

Rewiring monocyte glucose metabolism via C-type lectin signaling protects against disseminated candidiasis. / Domínguez-Andrés, Jorge; Arts, Rob J.W.; ter Horst, Rob; Gresnigt, Mark S.; Smeekens, Sanne P.; Ratter, Jacqueline M.; Lachmandas, Ekta; Boutens, Lily; van de Veerdonk, Frank L.; Joosten, Leo A.B.; Notebaart, Richard A.; Ardavín, Carlos; Netea, Mihai G.

In: PLoS Pathogens, Vol. 13, No. 9, e1006632, 18.09.2017.

Research output: Contribution to journalArticleAcademicpeer-review

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AU - Smeekens, Sanne P.

AU - Ratter, Jacqueline M.

AU - Lachmandas, Ekta

AU - Boutens, Lily

AU - van de Veerdonk, Frank L.

AU - Joosten, Leo A.B.

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AU - Ardavín, Carlos

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AB - Monocytes are innate immune cells that play a pivotal role in antifungal immunity, but little is known regarding the cellular metabolic events that regulate their function during infection. Using complementary transcriptomic and immunological studies in human primary monocytes, we show that activation of monocytes by Candida albicans yeast and hyphae was accompanied by metabolic rewiring induced through C-type lectin-signaling pathways. We describe that the innate immune responses against Candida yeast are energy-demanding processes that lead to the mobilization of intracellular metabolite pools and require induction of glucose metabolism, oxidative phosphorylation and glutaminolysis, while responses to hyphae primarily rely on glycolysis. Experimental models of systemic candidiasis models validated a central role for glucose metabolism in anti-Candida immunity, as the impairment of glycolysis led to increased susceptibility in mice. Collectively, these data highlight the importance of understanding the complex network of metabolic responses triggered during infections, and unveil new potential targets for therapeutic approaches against fungal diseases.

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Domínguez-Andrés J, Arts RJW, ter Horst R, Gresnigt MS, Smeekens SP, Ratter JM et al. Rewiring monocyte glucose metabolism via C-type lectin signaling protects against disseminated candidiasis. PLoS Pathogens. 2017 Sep 18;13(9). e1006632. https://doi.org/10.1371/journal.ppat.1006632