ArticlePLoS pathogens2013
Blocking TLR7- and TLR9-mediated IFN-α production by plasmacytoid dendritic cells does not diminish immune activation in early SIV infection.
Article in PLoS pathogens, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
42 citing papers in PubMed, 56 citations in OpenAlex.
- Plasmacytoid dendritic cells sense HIV replication before detectable viremia following treatment interruption.The Journal of clinical investigation · 2020Trial
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- BCG Immunotherapy in Equine Sarcoid Treatment: Mechanisms, Clinical Efficacy, and Challenges in Veterinary Oncology.Viruses · 2025Review
- DNA fromMicroorganisms · 2025Article
- The Antiviral Effects of Heat-KilledMicroorganisms · 2024Article
- DNA-Dependent Interferon Induction and Lung Inflammation inJournal of interferon & cytokine research : the official journal of the International Society for Interferon and Cytokine Research · 2023Article
- DNA Nanoflowers' Amelioration of Lupus Symptoms in Mice via Blockade of TLR7/9's Signal.International journal of molecular sciences · 2022Article
- Review
- Novel therapeutic strategies for chronic hepatitis B.Virulence · 2022Review
- The Role of Toll-Like Receptors in Retroviral Infection.Microorganisms · 2020Review
- TLR7 dosage polymorphism shapes interferogenesis and HIV-1 acute viremia in women.JCI insight · 2020Article
- When Dendritic Cells Go Viral: The Role of Siglec-1 in Host Defense and Dissemination of Enveloped Viruses.Viruses · 2019Review
- A pathogenic role of plasmacytoid dendritic cells in autoimmunity and chronic viral infection.The Journal of experimental medicine · 2019Review
- Role of Dendritic Cells in Natural Immune Control of HIV-1 Infection.Frontiers in immunology · 2019Review
- A requirement for slc15a4 in imiquimod-induced systemic inflammation and psoriasiform inflammation in mice.Scientific reports · 2018Article
- Inhibition of p38 MAPK in combination with ART reduces SIV-induced immune activation and provides additional protection from immune system deterioration.PLoS pathogens · 2018Article
- Distinct biomarker signatures in HIV acute infection associate with viral dynamics and reservoir size.JCI insight · 2018Article
- Type I interferon and HIV: Subtle balance between antiviral activity, immunopathogenesis and the microbiome.Cytokine & growth factor reviews · 2018Review
- Interferon-α Subtypes As an Adjunct Therapeutic Approach for Human Immunodeficiency Virus Functional Cure.Frontiers in immunology · 2018Review
- Assessing immune aging in HIV-infected patients.Virulence · 2017Review
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
Persistent production of type I interferon (IFN) by activated plasmacytoid dendritic cells (pDC) is a leading model to explain chronic immune activation in human immunodeficiency virus (HIV) infection but direct evidence for this is lacking. We used a dual antagonist of Toll-like receptor (TLR) 7 and TLR9 to selectively inhibit responses of pDC but not other mononuclear phagocytes to viral RNA prior to and for 8 weeks following pathogenic simian immunodeficiency virus (SIV) infection of rhesus macaques. We show that pDC are major but not exclusive producers of IFN-α that rapidly become unresponsive to virus stimulation following SIV infection, whereas myeloid DC gain the capacity to produce IFN-α, albeit at low levels. pDC mediate a marked but transient IFN-α response in lymph nodes during the acute phase that is blocked by administration of TLR7 and TLR9 antagonist without impacting pDC recruitment. TLR7 and TLR9 blockade did not impact virus load or the acute IFN-α response in plasma and had minimal effect on expression of IFN-stimulated genes in both blood and lymph node. TLR7 and TLR9 blockade did not prevent activation of memory CD4+ and CD8+ T cells in blood or lymph node but led to significant increases in proliferation of both subsets in blood following SIV infection. Our findings reveal that virus-mediated activation of pDC through TLR7 and TLR9 contributes to substantial but transient IFN-α production following pathogenic SIV infection. However, the data indicate that pDC activation and IFN-α production are unlikely to be major factors in driving immune activation in early infection. Based on these findings therapeutic strategies aimed at blocking pDC function and IFN-α production may not reduce HIV-associated immunopathology.
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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.