Monocyte glycolysis determines CD8+ T cell functionality in human Chagas disease

Area of Science:

• Immunology
• Metabolic Pathways
• Tropical Diseases

Background:

• Chagas disease, caused by Trypanosoma cruzi, is a major cause of heart failure in Latin America.
• Chronic infection leads to lifelong pathology and immune system dysregulation.

Purpose of the Study:

• To investigate the role of aerobic glycolysis in monocyte dysfunction and T cell impairment in chronic Chagas disease.
• To explore glycolysis inhibition as a therapeutic strategy.

Main Methods:

• Analysis of monocyte populations and hypoxia-inducible factor 1α (HIF-1α) in patients.
• Measurement of nitric oxide (NO) production and tyrosine nitration (TN) on CD8+ T cells.
• In vitro inhibition of glycolysis in peripheral blood mononuclear cells.

Main Results:

• Aerobic glycolysis activation in monocytes increases NO production and tyrosine nitration on CD8+ T cells.
• Nonclassical monocytes, expanded in patients, are a key source of NO.
• Glycolysis inhibition reduced inflammatory markers (IL-1β, NO) and improved CD8+ T cell function.

Conclusions:

• Glycolysis is a critical regulator of oxidative stress in monocytes during chronic Chagas disease.
• Targeting monocyte glycolysis may offer a novel therapeutic approach to restore immune function and mitigate Chagas disease pathology.