Interferon-γ differentially modulates the release of cytokines and chemokines in lipopolysaccharide- and pneumococcal cell wall-stimulated mouse microglia and macrophages


: Professor Uwe-Karsten Hanisch, University of Applied Sciences Lausitz, BCV, Großenhainer Straße 57, D-01968 Senftenberg, Germany


During bacterial infections of the CNS, activated microglia could support leucocyte recruitment to the brain through the synthesis of cyto- and chemokines. In turn, invading leucocytes may feedback on microglial cells to influence their chemokine release pattern. Here, we analyzed the capacity of interferon-γ (IFNγ) to serve as such a leucocyte-to-microglia signal. Production of cyto- and chemokines was stimulated in mouse microglia cultures by treatments with lipopolysaccharide (LPS) from Gram-negative Escherichia coli or cell walls from Gram-positive Streptococcus pneumoniae (PCW). IFNγ presence during the stimulation (0.1–100 ng/mL) modulated the patterns of LPS- and PCW-induced cyto- and chemokine release in a dose-dependent, potent and complex manner. While amounts of TNFα and IL-6 remained nearly unchanged, IFNγ enhanced the production of IL-12, MCP-1 and RANTES, but attenuated that of KC, MIP-1α and MIP-2. Release modulation was obtained with IFNγ preincubation (treatment of cells before LPS or PCW administration), coincubation and even delayed addition to an ongoing LPS or PCW stimulation. Together the changes observed for the microglial chemokine release under IFNγ would shift the chemoattractive profile from favouring neutrophils to a preferential attraction of monocytes and T lymphocyte populations – as actually seen during the course of bacterial meningitis. The findings support the view of activated microglia as a major intrinsic source for an instant production of a variety of chemokines and suggest that leucocyte-derived IFNγ could potentially regulate the microglial chemokine release pattern.