Regulation of CC chemokine receptor 5 and CD4 expression and human immunodeficiency virus type 1 replication in human macrophages and microglia by T helper type 2 cytokines.
Macrophages, microglia, and other mononuclear phagocytes serve as cellular reservoirs for viral persistence in patients with acquired immunodeficiency syndrome. To understand host mechanisms that affect human immunodeficiency virus type 1 (HIV-1) pathogenesis by modulating expression of coreceptors, cytokine regulation of CC chemokine receptor 5 (CCR5) and CD4 expression on monocytes, monocyte-derived macrophages (MDMs), and microglia was investigated. Interleukin (IL)-4 and IL-10 enhanced the entry and replication of HIV-1 in microglia through up-regulation of CD4 and CCR5 expression, respectively. IL-4 stimulated HIV-1 replication in MDMs but down-regulated CD4 and CCR5 expression and inhibited virus entry, whereas IL-10 had the opposite effects. Thus, mechanisms independent of CCR5 and CD4 expression levels are involved in pathways that regulate HIV-1 replication in MDMs. CCR5 up-regulation by IL-10 was associated with increased migration of microglia in response to macrophage inflammatory protein-1beta. These findings suggest that increased production of T helper type 2 cytokines in the later stages of disease can enhance virus entry and replication in mononuclear phagocytes and facilitate chemotactic migration.
Wang
Jianbin
J
Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115, USA.
Crawford
Keith
K
Yuan
Menglan
M
Wang
Hui
H
Gorry
Paul R
PR
Gabuzda
Dana
D
D015704:CD4 Antigens / Q000378:metabolism*; D002478:Cells, Cultured; D005786:Gene Expression Regulation; D015658:HIV Infections / Q000276:immunology / Q000821:virology; D015497:HIV-1 / Q000187:drug effects / Q000472:pathogenicity* / Q000502:physiology; D006801:Humans; D016753:Interleukin-10 / Q000494:pharmacology* / Q000502:physiology; D015847:Interleukin-4 / Q000494:pharmacology* / Q000502:physiology; D008264:Macrophages / Q000821:virology; D017628:Microglia / Q000821:virology; D009000:Monocytes / Q000821:virology; D019713:Receptors, CCR5 / Q000378:metabolism*; D018418:Th2 Cells / Q000378:metabolism; D014779:Virus Replication / Q000187:drug effects
D015704:CD4 Antigens; D019713:Receptors, CCR5; D016753:Interleukin-10; D015847:Interleukin-4