HIV-1 induces IL-10 production in human monocytes via a CD4-independent pathway.
In HIV-infected patients, increased levels of IL-10, mainly produced by virally infected monocytes, were reported to be associated with impaired cell-mediated immune responses. In this study, we investigated how HIV-1 induces IL-10 production in human monocytes. We found that CD14(+) monocytes infected by either HIV-1(213) (X4) or HIV-1(BaL) (R5) produced IL-10, IL-6, tumor necrosis factor-alpha (TNF-alpha), and to a lesser extent, IFN-gamma. However, the capacity of HIV-1 to induce these cytokines was not dependent on virus replication since UV-inactivated HIV-1 induced similar levels of these cytokines. In addition, soluble HIV-1 gp160 could induce CD14(+) monocytes to produce IL-10 but at lower levels. Cross-linking CD4 molecules (XLCD4) with anti-CD4 mAbs and goat anti-mouse IgG (GAM) resulted in high levels of IL-6, TNF-alpha and IFN-gamma but no IL-10 production by CD14(+) monocytes. Interestingly, neither anti-CD4 mAbs nor recombinant soluble CD4 (sCD4) receptor could block IL-10 secretion induced by HIV-1(213), HIV-1(BaL) or HIV-1 gp160 in CD14(+) monocytes, whereas anti-CD4 mAb or sCD4 almost completely blocked the secretion of the other cytokines. Furthermore, HIV-1(213) could induce IL-10 mRNA expression in CD14(+) monocytes while XLCD4 by anti-CD4 mAb and GAM failed to do so. As with IL-10 protein levels, HIV-1(213)-induced IL-10 mRNA expression in CD14(+) monocytes could not be inhibited by anti-CD4 mAb or sCD4. Taken together, HIV-1 binding to CD14(+) monocytes can induce CD4-independent IL-10 production at both mRNA and protein levels. This finding suggests that HIV induces the immunosuppressive IL-10 production in monocytes and is not dependent on CD4 molecules and that interference with HIV entry through CD4 molecules may have no impact on counteracting the effects of IL-10 during HIV infection.
Ji
Jiaxiang
J
Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX 77555-1070, USA.
Sahu
Gautam K
GK
Braciale
Vivian L
VL
Cloyd
Miles W
MW
D000906:Antibodies; D000911:Antibodies, Monoclonal; D015704:CD4 Antigens / Q000032:analysis; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis; D019302:HIV Envelope Protein gp160 / Q000494:pharmacology; D015658:HIV Infections / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D016753:Interleukin-10 / Q000096:biosynthesis* / Q000276:immunology; D018950:Lipopolysaccharide Receptors / Q000032:analysis; D009000:Monocytes / Q000187:drug effects / Q000276:immunology* / Q000821:virology; D011994:Recombinant Proteins / Q000494:pharmacology
D000906:Antibodies; D000911:Antibodies, Monoclonal; D015704:CD4 Antigens; D016207:Cytokines; D019302:HIV Envelope Protein gp160; D018950:Lipopolysaccharide Receptors; D011994:Recombinant Proteins; D016753:Interleukin-10