-
Views
-
Cite
Cite
Ankita Garg, Pratima Rawat, Stephen A. Spector, Interleukin 23 Produced by Myeloid Dendritic Cells Contributes to T-Cell Dysfunction in HIV Type 1 Infection by Inducing SOCS1 Expression, The Journal of Infectious Diseases, Volume 211, Issue 5, 1 March 2015, Pages 755–768, https://doi.org/10.1093/infdis/jiu523
- Share Icon Share
Abstract
The mechanism of myeloid dendritic cell (mDC)–mediated impaired T-cell function was investigated during human immunodeficiency virus type 1 (HIV-1) infection. HIV or gp120 were found to inhibit lipopolysaccharide-induced mDC maturation and cause defects in allogeneic T-cell proliferation, interleukin 2 and interferon γ (IFN-γ) production, and phosphorylated STAT1 expression. gp120-treated mDCs downregulated autologous T-cell proliferation and IFN-γ production against a peptide pool consisting of cytomegalovirus, Epstein-Barr virus, and influenza virus (CEF). These T-cell defects were associated with a decrease in production of the T-helper type 1–polarizing cytokine interleukin 12p70 and an increase in interleukin 23 (IL-23) production by gp120-treated mDCs. gp120-induced IL-23 upregulated suppressor of cytokine signaling 1 (SOCS1) protein in T cells, which inhibited IFN-γ production and killing of CEF-pulsed monocytes. These effector functions were recovered by silencing SOCS1 in T cells. Furthermore, we observed IL-23–induced SOCS1 binding to the IFN-γ transcription complex. These results identify SOCS1 as a novel target to improve the immune function in HIV-infected persons.