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

Glia. 2002 Aug;39(2):174-83. doi: 10.1002/glia.10095.


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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • AIDS Dementia Complex / immunology*
  • AIDS Dementia Complex / metabolism
  • AIDS Dementia Complex / virology
  • Adjuvants, Immunologic / pharmacology
  • Brain / immunology*
  • Brain / pathology
  • Brain / virology
  • Cell Division / drug effects
  • Cell Division / immunology
  • Cells, Cultured
  • Chemokine CCL3
  • Chemokine CCL4
  • Chemokine CCL5 / immunology
  • Chemokine CCL5 / metabolism
  • Chemokines, CC / genetics
  • Chemokines, CC / immunology*
  • Chemokines, CC / metabolism
  • Dose-Response Relationship, Drug
  • Female
  • Fetus
  • Granulocyte-Macrophage Colony-Stimulating Factor / immunology*
  • Granulocyte-Macrophage Colony-Stimulating Factor / pharmacology
  • HIV Core Protein p24 / immunology
  • HIV Core Protein p24 / metabolism
  • HIV-1 / drug effects
  • HIV-1 / immunology*
  • HIV-1 / metabolism
  • Hot Temperature / adverse effects
  • Humans
  • Macrophage Activation / drug effects
  • Macrophage Activation / immunology
  • Macrophage Colony-Stimulating Factor / immunology*
  • Macrophage Colony-Stimulating Factor / pharmacology
  • Macrophage Inflammatory Proteins / immunology
  • Macrophage Inflammatory Proteins / metabolism
  • Microglia / drug effects
  • Microglia / immunology*
  • Microglia / virology
  • Pregnancy
  • Recombinant Fusion Proteins / drug effects
  • Recombinant Fusion Proteins / immunology
  • Virus Replication / drug effects
  • Virus Replication / immunology


  • Adjuvants, Immunologic
  • Chemokine CCL3
  • Chemokine CCL4
  • Chemokine CCL5
  • Chemokines, CC
  • HIV Core Protein p24
  • Macrophage Inflammatory Proteins
  • Recombinant Fusion Proteins
  • Macrophage Colony-Stimulating Factor
  • Granulocyte-Macrophage Colony-Stimulating Factor