HIV-1 gp120 activates the STAT3/interleukin-6 axis in primary human monocyte-derived dendritic cells

Manuela del Corno`, Gloria Donninelli, Barbara Varano, Letizia da Sacco, Andrea Masotti, Sandra Gessani

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Dendritic cells (DCs) are fundamental for the initiation of immune responses and are important players in AIDS immunopathogenesis. The modulation of DC functional activities represents a strategic mechanism for HIV-1 to evade immune surveillance. Impairment of DC function may result from bystander effects of HIV-1 envelope proteins independently of direct HIV-1 infection. In this study, we report that exposure of immature monocyte-derived DCs (MDDCs) to HIV-1 R5 gp120 resulted in the CCR5-dependent production of interleukin-6 (IL-6) via mitogen-activated protein kinase (MAPK)/ NF-κB pathways. IL-6 in turn activated STAT3 by an autocrine loop. Concomitantly, gp120 promoted an early activation of STAT3 that further contributed to IL-6 induction. This activation paralleled a concomitant upregulation of the STAT3 inhibitor PIAS3. Notably, STAT3/IL-6 pathway activation was not affected by the CCR5-specific ligand CCL4. These results identify STAT3 as a key signaling intermediate activated by gp120 in MDDCs and highlight the existence of a virus-induced dysregulation of the IL-6/STAT3 axis. HIV-1 gp120 signaling through STAT3 may provide an explanation for the impairment of DC function observed upon HIV exposure.

Original languageEnglish
Pages (from-to)11045-11055
Number of pages11
JournalJournal of Virology
Issue number19
Publication statusPublished - 2014

ASJC Scopus subject areas

  • Immunology
  • Virology


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