Astrocytes Contacting HIV-1-Infected Macrophages Increase the Release of CCL2 in Response to the HIV-1-Dependent Enhancement of Membrane-Associated TNFα in Macrophages

The presence of human immunodeficiency virus (HIV)-infected macrophages in the parenchyma of central nervous system is an hallmark of acquired immunodeficiency syndrome-related neuroinflammation. Once penetrated the blood brain barrier (BBB), macrophages closely interact with astrocytes, beginning with those lying beneath the BBB endothelium. By investigating the consequences of the cell cell interaction between HIV-infected macrophages and astrocytes, we observed that the HIV-1 expression in macrophagic cells correlated with increased chemotactic activity in supernatants of astroglial cells. Gene array analysis revealed an impressive increase in the transcription of the gene for the CCL2/MCP-1 chemokine in astroglial cells isolated from HIV-1-infected co-cultures compared with cells from uninfected co-cultures. This phenomenon coupled with the increase in CCL2 release and depended on the cell cell contact. In addition, it was a consequence of the HIV-1-induced enhancement of membrane-associated tumor necrosis factor-alpha in macrophagic cells, and correlated with increased levels of nuclear factor kappaB activation in astroglial cells. These observations could mirror a mechanism of recruitment of leukocytes through the BBB, likely contributing to the increase in both viral load and inflammation in central nervous system of HIV-infected patients. (C) 2010 Wiley-Liss, Inc.