Interferon-gamma upregulates CCR5 expression in cord and adult blood mononuclear phagocytes

The C-C chemokine receptors CCR5 and CCR3 are fusion coreceptors for human immunodeficiency virus (HIV) entry into macrophages. The regulation of thei r expression influences infectivity by HIV. We report here that interferon- gamma (IFN-gamma) a cytokine that has bidirectional effects on HIV infectio n of macrophages. significantly upregulated CCR5 and CCR3 cell surface expr ession in human mononuclear phagocytes isolated from placental cord blood a nd adult peripheral blood. Monocytes treated with IFN-gamma showed increase d chemotaxis to the CCR5 ligands macrophage inflammatory protein-let (MIP-l a) and MIP-1 beta, confirming the functional relevance of IFN-gamma-induced CCR5 expression. However, IFN-gamma suppressed HIV entry into macrophages. interestingly, we demonstrated that IFN-gamma inhibited cell surface expre ssion of CD4, the major receptor for HIV. This finding may explain the supp ressive effect of IFN-gamma on HIV entry into macrophages, despite its enha ncing effect on the expression of CCR5 and CCR3 by these cells. In addition , IFN-gamma-induced secretion of C-C chemokines (RANTES, MIP-1 alpha, and M IP-1 beta) by mononuclear phagocytes may also suppress HIV entry into macro phages. These data provide further evidence for cytokine-mediated regulatio n of CCR5 expression and are consistent with a novel paradigm in which cyto kines regulate HIV infection and leukocyte migration by reciprocal and oppo sing effects on the expression of CD4 and chemokine receptors. (C) 1999 by The American Society of Hematology.