International Immunology Advance Access originally published online on June 3, 2005
International Immunology 2005 17(6):729-736; doi:10.1093/intimm/dxh252
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HIV-1 induces IL-10 production in human monocytes via a CD4-independent pathway
Department of Microbiology and Immunology, University of Texas Medical Branch at Galveston, Galveston, TX 77555-1070, USA
Correspondence to: M. W. Cloyd; E-mail: mcloyd{at}utmb.edu
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-1213 (X4) or HIV-1BaL (R5) produced IL-10, IL-6, tumor necrosis factor-
(TNF-), and to a lesser extent, IFN-
. 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- and IFN- 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-1213, HIV-1BaL or HIV-1 gp160 in CD14+ monocytes, whereas anti-CD4 mAb or sCD4 almost completely blocked the secretion of the other cytokines. Furthermore, HIV-1213 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-1213-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.
Keywords: CD4-independent, HIV-1, IL-10, monocytes
Transmitting editor: R. Steinman
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