Microglia digest Staphylococcus aureus into low molecular weight biologically active compounds

Area of Science:

• Neuroimmunology
• Cellular Immunology

Background:

• Excess sleep and fever are central nervous system (CNS) responses during infection, linked to cytokine production.
• Peripheral macrophages digest bacteria, releasing muramyl peptides that stimulate cytokine production, but CNS phagocyte function was unclear.

Purpose of the Study:

• To investigate if microglia, the resident phagocytes of the CNS, can digest bacteria and produce substances that influence CNS functions.

Main Methods:

• Primary microglia cultures phagocytized and digested radiolabeled Staphylococcus aureus.
• Released low molecular weight substances were purified and tested for biological activity.
• Substances were injected intracerebroventricularly into rabbits to assess effects on sleep and temperature.
• Effects on human monocyte cytokine production (interleukin-1, tumor necrosis factor, interleukin-1 receptor antagonist) were measured.

Main Results:

• Microglia digested Staphylococcus aureus, releasing biologically active substances.
• These substances induced excess non-rapid eye movement sleep, increased electroencephalographic slow-wave activity, and elevated brain temperature in rabbits.
• The substances stimulated the production of interleukin-1, tumor necrosis factor, and interleukin-1 receptor antagonist in human monocytes.

Conclusions:

• Microglia possess fundamental macrophage functions, including bacterial digestion and the release of immunomodulatory substances.
• These findings implicate microglia as resident immunocompetent cells within the CNS, capable of initiating acute phase responses.