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

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

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
Volume88
Issue number19
DOIs
Publication statusPublished - 2014

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dendritic cells
Human immunodeficiency virus 1
interleukin-6
monocytes
Dendritic Cells
HIV-1
Monocytes
Interleukin-6
Bystander Effect
Proto-Oncogene Proteins c-akt
Mitogen-Activated Protein Kinases
mitogen-activated protein kinase
HIV Infections
Acquired Immunodeficiency Syndrome
Up-Regulation
immatures
immune response
HIV
Ligands
Viruses

ASJC Scopus subject areas

  • Immunology
  • Virology

Cite this

HIV-1 gp120 activates the STAT3/interleukin-6 axis in primary human monocyte-derived dendritic cells. / del Corno`, Manuela; Donninelli, Gloria; Varano, Barbara; da Sacco, Letizia; Masotti, Andrea; Gessani, Sandra.

In: Journal of Virology, Vol. 88, No. 19, 2014, p. 11045-11055.

Research output: Contribution to journalArticle

del Corno`, M, Donninelli, G, Varano, B, da Sacco, L, Masotti, A & Gessani, S 2014, 'HIV-1 gp120 activates the STAT3/interleukin-6 axis in primary human monocyte-derived dendritic cells', Journal of Virology, vol. 88, no. 19, pp. 11045-11055. https://doi.org/10.1128/JVI.00307-14
del Corno`, Manuela ; Donninelli, Gloria ; Varano, Barbara ; da Sacco, Letizia ; Masotti, Andrea ; Gessani, Sandra. / HIV-1 gp120 activates the STAT3/interleukin-6 axis in primary human monocyte-derived dendritic cells. In: Journal of Virology. 2014 ; Vol. 88, No. 19. pp. 11045-11055.
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