Glutamine alleviates Staphylococcus aureus-induced mastitis by modulating macrophage polarisation

Area of Science:

• Veterinary Immunology
• Microbiology
• Animal Nutrition

Background:

• Mastitis, a significant dairy industry issue, is frequently caused by Staphylococcus aureus.
• Gut microbiota disruption has been linked to increased mastitis susceptibility due to reduced glutamine levels.

Purpose of the Study:

• To investigate the potential of oral glutamine in regulating macrophage function and mitigating Staphylococcus aureus mastitis.
• To elucidate the underlying mechanisms involving glutamine metabolites and immune cell polarization.

Main Methods:

• Oral administration of glutamine and alpha-ketoglutaric acid (αKG) in a mouse model of Staphylococcus aureus mastitis.
• Assessment of mastitis severity, blood-milk barrier integrity, and macrophage polarization (M2-type).
• In vitro studies on macrophage autophagy, JAK/STAT pathway activation, and SOCS3 expression.

Main Results:

• Glutamine attenuated S. aureus mastitis, preserved blood-milk barrier function, and increased M2 macrophages.
• αKG, a glutamine metabolite, also enhanced M2 macrophage polarization and reduced mastitis severity.
• αKG promoted autophagy via oxidative phosphorylation, regulating SOCS3 and activating the JAK-STAT pathway, thereby promoting M2 polarization.

Conclusions:

• Glutamine and αKG play crucial roles in mammary gland resistance to S. aureus infection.
• The mechanism involves αKG-induced autophagy and JAK-STAT pathway activation, promoting M2 macrophage polarization.
• Dietary glutamine represents a potential intervention for mastitis prevention and treatment in dairy cows.