Complement Has Brains-Do Intracellular Complement and Immunometabolism Cooperate in Tissue Homeostasis and Behavior?

Area of Science:

• Immunology
• Metabolic pathways
• Neuroscience

Background:

• The classical complement system mediates host protection via innate and adaptive immunity.
• Recent discoveries reveal an intracellular complement system, the complosome, regulating immune cell metabolism.
• Complosome components, like C3, are induced in monocytes and T cells entering tissues.

Purpose of the Study:

• To review complement-driven metabolic reprogramming in immune cells.
• To discuss the role of the complosome, cell metabolism, and IFN-γ in immunity and behavior.
• To explore the connection between immune cells, IFN-γ, and brain function.

Main Methods:

• Literature review of current research on intracellular complement.
• Analysis of studies on immune cell metabolism and cytokine function.
• Synthesis of findings linking immunity, metabolism, and neurological processes.

Main Results:

• Intracellular complement activity reprograms immune cells, increasing glycolysis and OXPHOS.
• This metabolic shift drives pro-inflammatory cytokine IFN-γ production.
• Reduced complosome activity impairs immune cell function and tissue immunity.

Conclusions:

• The complosome is a key regulator of immune cell metabolic reprogramming and function.
• A conserved interplay between the complosome, metabolism, and IFN-γ may regulate immunity and behavior.
• Further research is needed to elucidate the complosome's role in neurological function.