GM-CSF and M-CSF modulate beta-chemokine and HIV-1 expression in microglia

TitleGM-CSF and M-CSF modulate beta-chemokine and HIV-1 expression in microglia
Publication TypeJournal Article
Year of Publication2002
AuthorsSi, Q, Cosenza-Nashat, MA, Zhao, ML, Goldstein, H, Lee, SC
Date Published08/2002
KeywordsAdjuvants, CC, Cell Division, Cells, Chemokine CCL3, Chemokine CCL4, Chemokine CCL5, Chemokines, Cultured, Dose-Response Relationship, Drug, External, Granulocyte-Macrophage Colony-Stimulating Factor, Heat, Immunologic, Macrophage Activation, Macrophage C

Significant numbers of patients with acquired immunodeficiency syndrome (AIDS) develop CNS infection primarily in macrophages and microglial cells. Therefore, the regulation of human immunodeficiency virus type 1 (HIV-1) infection and activation of the brain mononuclear phagocytes subsequent to infection are important areas of investigation. In the current report, we studied the role of granulocyte-macrophage colony-stimulating factor (GM-CSF) and macrophage-CSF (M-CSF) in the expression of antiviral beta-chemokines and HIV-1 p24 in cultures of primary human fetal microglia. We found that stimulation with GM-CSF or M-CSF induced macrophage inflammatory proteins (MIP-1alpha and MIP-1beta) and augmented RANTES expression, after HIV-1 infection of microglia. This was not due to the effect of GM-CSF on viral expression because GM-CSF was neither necessary nor stimulatory for viral infection, nor did GM-CSF enhance the expression of env-pseudotyped reporter viruses. Blocking GM-CSF-induced microglial proliferation by nocodazole had no effect on beta-chemokine or p24 expression. The functional significance of the GM-CSF-induced beta-chemokines was suggested by the finding that, in the presence of GM-CSF, exogenous beta-chemokines lost their anti-HIV-1 effects. We further show that although HIV-1-infected microglia produced M-CSF, they failed to produce GM-CSF. In vivo, GM-CSF expression was localized to activated astrocytes and some inflammatory cells in HIV-1 encephalitis, suggesting paracrine activation of microglia through GM-CSF. Our results demonstrate a complex interplay between CSFs, chemokines, and virus in microglial cells and may have bearing on the interpretation of data derived in vivo and in vitro.