Memory CD8(+) T Cells Require Increased Concentrations of Acetate Induced by Stress for Optimal Function

Area of Science:

• Immunology
• Metabolic Biochemistry

Background:

• Systemic metabolic changes during acute infections and their effect on immune cells are not well understood.
• Acetate accumulation in serum during bacterial infections is a known phenomenon.

Purpose of the Study:

• To investigate the functional role of increased serum acetate concentrations on memory CD8(+) T cell function during acute bacterial infections.
• To elucidate the underlying molecular mechanisms by which acetate influences CD8(+) T cell metabolism and activity.

Main Methods:

• In vitro and in vivo studies using CD8(+) T cells.
• Measurement of serum acetate levels.
• Analysis of cellular acetyl-coenzyme A pool expansion.
• Assessment of GAPDH acetylation and activity.
• Glycolysis assays.
• Murine Listeria monocytogenes infection model.

Main Results:

• Serum acetate levels increase rapidly during systemic bacterial infections.
• Elevated acetate concentrations are essential for optimal memory CD8(+) T cell function.
• Acetate uptake by CD8(+) T cells expands acetyl-coenzyme A, enhances GAPDH acetylation, and boosts glycolysis.
• Acetate-augmented CD8(+) T cells provide superior immune control in vivo.

Conclusions:

• Increased systemic acetate during infection is a key metabolic signal integrated by memory CD8(+) T cells.
• Acetate enhances CD8(+) T cell metabolic and functional capacity through post-translational modification of GAPDH.
• This metabolic reprogramming contributes to effective immune responses and host defense.