Glatiramer acetate stimulates phagocytosis and intracellular killing of Escherichia coli by macrophages and microglial cells

Background In contrast to other medications used for the treatment of multiple sclerosis (MS), glatiramer acetate (GA), a synthetic polypeptide, has not been associated with an increased risk of infections. We studied the effect of GA on innate immune cells and its ability to ingest and kill bacteria. Methods GA was co-incubated with peritoneal macrophages and microglial cells from wild-type C57BL/6 and interleukin (IL)-10 -/- mice. Subsequently, phagocytosis and intracellular killing of encapsulated Escherichia ( E .) coli K1 by these phagocytes was analyzed. Using microglia from wild-type mice, IL10 was blocked by the addition of antibodies. GA was administered in vivo to wild-type and IL10 -/- mice. Afterwards, peritoneal macrophages were isolated and tested for their phagocytic capacity. Results GA increased phagocytosis in a concentration- and time-dependent manner of E. coli by macrophages and microglia isolated from wild-type mice. GA also increases the intracellular killing of E. coli . Macrophages from IL10-/- mice were one order of magnitude less susceptible to GA. Blocking of IL10 reduced phagocytosis in microglia in a concentration-dependent manner. GA stimulated phagocytosis also in macrophages from old mice. The in vivo administration of GA increased the phagocytic capacity of wild-type but not IL10-/- macrophages ex vivo . Conclusions As a consequence of the increased threat by multi-resistant bacteria, immunomodulators with few side effects, which are able to stimulate the phagocytosis and killing of bacteria, are highly desirable. GA stimulates the phagocytosis and intracellular killing of pathogenic bacteria. Due to its low toxicity even during long-term treatment, GA is an excellent candidate to increase the resistance of patients to infection, potentially reducing the amount of antibiotics prescribed.