Microglia digest Staphylococcus aureus into low molecular weight biologically active compounds

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.