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Microglia digest Staphylococcus aureus into low molecular weight biologically active compounds
E F Fincher1, L Johannsen, L Kapás
1Department of Physiology and Biophysics, University of Tennessee, Memphis 38163, USA.
Abstract:
Excess sleep and fever are central nervous system (CNS) facets of the acute phase response; these responses are induced by microbial products, such as muramyl peptides, via their ability to enhance cytokine production. Although peripheral macrophages are known to digest bacteria, thereby releasing muramyl peptides that, in turn, stimulate cytokine production, it was unknown whether CNS phagocytes such as microglia also had this capacity. Primary cultures of microglia were allowed to phagocytize and digest Staphylococcus aureus radiolabeled with a cell wall-specific marker. Radiolabeled low molecular weight substances released into the culture medium were partially purified and tested for the ability to induce excess sleep, fever, and cytokine production. These substances increased non-rapid eye movement sleep, electroencephalographic slow-wave activity, and brain temperature after intracerebroventricular injection into rabbits. They also induced interleukin-1, tumor necrosis factor, and the interleukin-1 receptor antagonist production in human monocytes. Results suggest that microglia perform fundamental macrophage functions and further implicate microglia as resident immunocompetent cells.
Insights
Microglia, brain immune cells, digest bacteria and release substances that induce sleep and fever. This suggests microglia have essential macrophage functions within the central nervous system (CNS).
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.