ArticlePLoS pathogens2014
Plasmacytoid dendritic cells suppress HIV-1 replication but contribute to HIV-1 induced immunopathogenesis in humanized mice.
Article in PLoS pathogens, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 76 papers.
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Who cites it
76 citing papers in PubMed, 101 citations in OpenAlex.
- Antiviral Innate Immune Activation in HIV-Infected Adults Negatively Affects H1/IC31-Induced Vaccine-Specific Memory CD4+ T Cells.Clinical and vaccine immunology : CVI · 2015Trial
- Febrile-range temperature selectively limits sustained pDC-Derived IFN-α via attenuation of STAT1-Dependent feedback signaling.Cell insight · 2026Article
- Article
- CD4-Based Chimeric Antigen Receptor (CAR)-T Cells With Resistance to HIV-1 Infection and Enhanced Anti-HIV Efficacy: Covalent Interaction Between CD4-CAR and HIV-1 Envelope Glycoprotein.Journal of medical virology · 2026Article
- Dysfunction of the plasmacytoid dendritic cells in enterovirus 71-induced HFMD affecting children.BMC immunology · 2026Article
- Targeting the pDC/IFN-I axis in HIV-1 immunotherapy.Current opinion in HIV and AIDS · 2026Review
- HIV-1 Nef inhibits the JAK/STAT signaling pathway by inducing proteasomal degradation of STAT1.PloS one · 2026Article
- Persistent Type I Interferon Signaling Impairs Innate Lymphoid Cells During HIV-1 Infection Under Suppressive ART.Viruses · 2025Article
- CD24-Fc resolves inflammation and enhances anti-HIV CD8 T cells with polyfunctionality during HIV-1 infection under cART.PLoS pathogens · 2025Article
- Review
- The TLR7/IRF-5 axis sensitizes memory CD4+ T cells to Fas-mediated apoptosis during HIV-1 infection.JCI insight · 2023Article
- Type I interferons and TGF-β cooperate to induce liver fibrosis during HIV-1 infection under antiretroviral therapy.JCI insight · 2022Article
- Extracellular Microvesicles Released From Brain Endothelial Cells are Detected in Animal Models Of HIV-1 Signifying Unresolved Inflammation.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2021Article
- A TLR7 antagonist restricts interferon-dependent and -independent immunopathology in a mouse model of severe influenza.The Journal of experimental medicine · 2021Article
- Preclinical Evaluation of B7-H3-specific Chimeric Antigen Receptor T Cells for the Treatment of Acute Myeloid Leukemia.Clinical cancer research : an official journal of the American Association for Cancer Research · 2021Article
- Perspectives on Non-BLT Humanized Mouse Models for Studying HIV Pathogenesis and Therapy.Viruses · 2021Review
- Plasmacytoid dendritic cells have divergent effects on HIV infection of initial target cells and induce a pro-retention phenotype.PLoS pathogens · 2021Article
- Humanized Mice as a Tool to Study Sepsis-More Than Meets the Eye.International journal of molecular sciences · 2021Review
- Distinct Features of Germinal Center Reactions in Macaques Infected by SIV or Vaccinated with a T-Dependent Model Antigen.Viruses · 2021Article
- TLR9- and CD40-Targeting Vaccination Promotes Human B Cell Maturation and IgG InductionFrontiers in immunology · 2021Article
16 more citing papers are in PubMed but not listed here.
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Authors and funding
9 authors at 4 institutions in 2 countries.
Funding
Abstract
The role of plasmacytoid dendritic cells (pDC) in human immunodeficiency virus type 1 (HIV-1) infection and pathogenesis remains unclear. HIV-1 infection in the humanized mouse model leads to persistent HIV-1 infection and immunopathogenesis, including type I interferons (IFN-I) induction, immune-activation and depletion of human leukocytes, including CD4 T cells. We developed a monoclonal antibody that specifically depletes human pDC in all lymphoid organs in humanized mice. When pDC were depleted prior to HIV-1 infection, the induction of IFN-I and interferon-stimulated genes (ISGs) were abolished during acute HIV-1 infection with either a highly pathogenic CCR5/CXCR4-dual tropic HIV-1 or a standard CCR5-tropic HIV-1 isolate. Consistent with the anti-viral role of IFN-I, HIV-1 replication was significantly up-regulated in pDC-depleted mice. Interestingly, the cell death induced by the highly pathogenic HIV-1 isolate was severely reduced in pDC-depleted mice. During chronic HIV-1 infection, depletion of pDC also severely reduced the induction of IFN-I and ISGs, associated with elevated HIV-1 replication. Surprisingly, HIV-1 induced depletion of human immune cells including T cells in lymphoid organs, but not the blood, was reduced in spite of the increased viral replication. The increased cell number in lymphoid organs was associated with a reduced level of HIV-induced cell death in human leukocytes including CD4 T cells. We conclude that pDC play opposing roles in suppressing HIV-1 replication and in promoting HIV-1 induced immunopathogenesis. These findings suggest that pDC-depletion and IFN-I blockade will provide novel strategies for treating those HIV-1 immune non-responsive patients with persistent immune activation despite effective anti-retrovirus treatment.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.