HIV-1 induces IL-10 production in human monocytes via a CD4-independent pathway

Jiaxiang Ji, Gautam K. Sahu, Vivian L. Braciale, Miles W. Cloyd

Research output: Contribution to journalArticle

24 Scopus citations

Abstract

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-α (TNF-α), and to a lesser extent, IFN-γ. 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-α and IFN-γ 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.

Original languageEnglish (US)
Pages (from-to)729-736
Number of pages8
JournalInternational immunology
Volume17
Issue number6
DOIs
StatePublished - Jun 1 2005

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Keywords

  • CD4-independent
  • HIV-1
  • IL-10
  • Monocytes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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