Species-specific metabolic reprogramming in human and mouse microglia during inflammatory pathway induction

Area of Science:

• Immunometabolism
• Cellular metabolism
• Neuroinflammation

Background:

• Metabolic reprogramming is crucial for immune cell function during inflammation.
• Oxidative phosphorylation (OXPHOS) to glycolysis switch is common, but human microglia data is scarce.
• Most studies use mouse models, limiting direct human relevance.

Purpose of the Study:

• To compare the metabolic reprogramming of mouse and human microglia.
• To investigate transcriptomic, proteomic, and metabolic profiles after Toll-like receptor 4 (TLR4) agonist lipopolysaccharide (LPS) challenge.
• To identify species-specific metabolic pathways in microglia.

Main Methods:

• Utilized transcriptomic, proteomic, and metabolic profiling.
• Compared primary mouse microglia with induced pluripotent stem cell (iPSC)-derived human microglia.
• Stimulated cells with the TLR4 agonist LPS.

Main Results:

• Both mouse and human microglia exhibited metabolic shifts and increased glycolytic gene expression upon LPS stimulation.
• Mouse microglia showed upregulation of hexokinases.
• Human microglia displayed upregulation of phosphofructokinases.

Conclusions:

• Microglia undergo significant metabolic reprogramming in response to inflammatory stimuli.
• Key enzymes in glycolysis differ between mouse and human microglia, indicating species-specific metabolic pathways.
• Understanding these species-specific differences is vital for effective translational research in neuroinflammation.