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Updated: Jan 11, 2026
Assessing the Innate Sensing of HIV-1 Infected CD4+ T Cells by Plasmacytoid Dendritic Cells Using an Ex vivo Co-culture System.
Published on: September 1, 2015
Targeting the pDC/IFN-I axis in HIV-1 immunotherapy
Lishan Su1, James Ahodantin, Guangming Li
1Division of Virology, Pathogenesis and Cancer, Institute of Human Virology, Department of Pharmacology and Physiology, University of Maryland School of Medicine, Baltimore, Maryland, USA.
Purpose Of Review:
Recent findings on the critical pathogenic role of inflammatory pDC and type 1 interferons (IFN-I) in HIV-1 pathogenesis in humanized mice and its correlation with inflammatory diseases in people living with HIV-1 (PLWH) suggest that targeting the pDC/IFN-I signaling pathway will reverse HIV-induced inflammation to treat HIV-associated end-organ diseases and rescue anti-HIV immunity to reduce or control HIV-1 reservoirs.
Recent Findings:
In both humanized mice and in PBMC from people living with HIV-1 (PLWH), depletion of pDC or inhibition of IFN-I signaling resolves IFN-associated inflammation, rescues anti-HIV T cell functions and reduces HIV-1 reservoir cells. In humanized mice with HIV-1 persistent infection under effective HAART, persistent pDC activation and IFN-I signaling has been shown to induce HIV-associated tissue injury and anti-HIV T cell impairment. in HIV-infected mice with effective HAART, pDC depletion phenocopies what is achieved with blocking IFN-I signaling in reversing HIV-induced inflammation, rescuing anti-HIV T cells and reducing HIV-1 reservoirs. Interestingly, in both humanized mice and in PBMC from PLWH, depletion of pDC or inhibition of IFN-I signaling rescues anti-HIV TCF1+ (T cell factor 1) PD1+ (programmed cell death protein 1) CD8 T cell functions to enhance the effect of PD1 immune checkpoint inhibitor (ICI) to reduce HIV-1 reservoir cells.
Summary:
These findings functionally define the role of the pDC/IFN-I pathway in HIV-associated inflammation, HIV-1 reservoir persistence and end-organ diseases, and suggest that inhibiting pDC or blocking IFN-I signaling will provide a novel therapeutic strategy to reverse inflammation-associated diseases and to rescue anti-HIV immunity that cooperates with PD1 ICI effect to reduce or control HIV-1 reservoirs.
