Skip to Content
Merck
  • Fungal sensing enhances neutrophil metabolic fitness by regulating antifungal Glut1 activity.

Fungal sensing enhances neutrophil metabolic fitness by regulating antifungal Glut1 activity.

Cell host & microbe (2022-03-23)
De-Dong Li, Chetan V Jawale, Chunsheng Zhou, Li Lin, Giraldina J Trevejo-Nunez, Syed A Rahman, Steven J Mullet, Jishnu Das, Stacy G Wendell, Greg M Delgoffe, Michail S Lionakis, Sarah L Gaffen, Partha S Biswas
ABSTRACT

Combating fungal pathogens poses metabolic challenges for neutrophils, key innate cells in anti-Candida albicans immunity, yet how host-pathogen interactions cause remodeling of the neutrophil metabolism is unclear. We show that neutrophils mediate renal immunity to disseminated candidiasis by upregulating glucose uptake via selective expression of glucose transporter 1 (Glut1). Mechanistically, dectin-1-mediated recognition of β-glucan leads to activation of PKCδ, which triggers phosphorylation, localization, and early glucose transport by a pool of pre-formed Glut1 in neutrophils. These events are followed by increased Glut1 gene transcription, leading to more sustained Glut1 accumulation, which is also dependent on the β-glucan/dectin-1/CARD9 axis. Card9-deficient neutrophils show diminished glucose incorporation in candidiasis. Neutrophil-specific Glut1-ablated mice exhibit increased mortality in candidiasis caused by compromised neutrophil phagocytosis, reactive oxygen species (ROS), and neutrophil extracellular trap (NET) formation. In human neutrophils, β-glucan triggers metabolic remodeling and enhances candidacidal function. Our data show that the host-pathogen interface increases glycolytic activity in neutrophils by regulating Glut1 expression, localization, and function.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
WZB-117, ≥98% (HPLC)
Sigma-Aldrich
Zymosan A from Saccharomyces cerevisiae, for inducing inflamatory response
Sigma-Aldrich
Anti-GLUT-1 Antibody, CT, from rabbit, purified by affinity chromatography
Sigma-Aldrich
GW5074, powder
Sigma-Aldrich
Anti-phospho GLUT-1 Antibody (Ser226), from rabbit, purified by affinity chromatography