Activation induces shift in nutrient utilization that differentially impacts cell functions in human neutrophils

Area of Science:

• Immunology
• Cellular Metabolism
• Biochemistry

Background:

• Neutrophils are critical innate immune cells.
• Their functions depend on diverse metabolic pathways.
• Understanding neutrophil nutrient utilization is vital for health.

Purpose of the Study:

• To investigate nutrient contributions to neutrophil metabolism.
• To examine metabolic shifts upon neutrophil activation.
• To link metabolic changes to specific neutrophil functions.

Main Methods:

• In vivo and ex vivo isotopic tracing in human neutrophils.
• Analysis of nutrient utilization under resting and activated states.
• Correlation of metabolic shifts with neutrophil functions like oxidative burst, NETosis, phagocytosis, migration, and fungal control.

Main Results:

• Resting neutrophils primarily use glycogen; activated neutrophils switch to extracellular glucose.
• Increased glucose uptake via GLUT1 drives this metabolic shift.
• Specific neutrophil functions show differential dependence on glucose or glycogen.

Conclusions:

• Neutrophil metabolism is dynamic and adaptable.
• Metabolic remodeling significantly shapes neutrophil functions.
• This study provides quantitative insights into neutrophil metabolic plasticity and its health relevance.