ArticleThe Journal of clinical investigation2008
TNF-alpha and TLR agonists increase susceptibility to HIV-1 transmission by human Langerhans cells ex vivo.
Article in The Journal of clinical investigation, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 72 papers, 2 of them syntheses that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
72 citing papers in PubMed, 2 syntheses or guidelines pooled it, 128 citations in OpenAlex.
- Pooled it
- Sexually transmitted hepatitis C virus infections: current trends, and recent advances in understanding the spread in men who have sex with men.Journal of the International AIDS Society · 2019Pooled it
- Langerhans cells as targets of rabies virus immune evasion.The Journal of general virology · 2026Article
- Social, microbial, and immune factors linking bacterial vaginosis and infectious diseases.The Journal of clinical investigation · 2025Review
- The spatial biology of HIV infection.PLoS pathogens · 2025Review
- Prevotella timonensis Bacteria Associated With Vaginal Dysbiosis Enhance Human Immunodeficiency Virus Type 1 Susceptibility Of Vaginal CD4+ T Cells.The Journal of infectious diseases · 2024Article
- Immune activation of vaginal human Langerhans cells increases susceptibility to HIV-1 infection.Scientific reports · 2023Article
- Vaginal bacterium Prevotella timonensis turns protective Langerhans cells into HIV-1 reservoirs for virus dissemination.The EMBO journal · 2022Article
- Review
- CGRP inhibits human Langerhans cells infection with HSV by differentially modulating specific HSV-1 and HSV-2 entry mechanisms.Mucosal immunology · 2022Article
- Contribution of Sex Differences to HIV Immunology, Pathogenesis, and Cure Approaches.Frontiers in immunology · 2022Review
- Alarmin S100A9 restricts retroviral infection by limiting reverse transcription in human dendritic cells.The EMBO journal · 2021Article
- Circumcision as an Intervening Strategy against HIV Acquisition in the Male Genital Tract.Pathogens (Basel, Switzerland) · 2021Review
- HIV-1 subverts the complement system in semen to enhance viral transmission.Mucosal immunology · 2021Article
- HIV-Exposed Seronegative Sex Workers Express Low T-Cell Activation and an Intact Ectocervical Tissue Microenvironment.Vaccines · 2021Article
- Autophagy-enhancing drugs limit mucosal HIV-1 acquisition and suppress viral replication ex vivo.Scientific reports · 2021Article
- Human TRIM5α: Autophagy Connects Cell-Intrinsic HIV-1 Restriction and Innate Immune Sensor Functioning.Viruses · 2021Review
- Complement-Opsonized HIV Modulates Pathways Involved in Infection of Cervical Mucosal Tissues: A Transcriptomic and Proteomic Study.Frontiers in immunology · 2021Article
- The Role of Toll-Like Receptors in Retroviral Infection.Microorganisms · 2020Review
- Syndecan 4 Upregulation on Activated Langerhans Cells Counteracts Langerin Restriction to Facilitate Hepatitis C Virus Transmission.Frontiers in immunology · 2020Article
12 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
Abstract
Genital coinfections increase an individual's risk of becoming infected with HIV-1 by sexual contact. Several mechanisms have been proposed to explain this, such as the presence of ulceration and bleeding caused by the coinfecting pathogen. Here we demonstrate that Langerhans cells (LCs) are involved in the increased susceptibility to HIV-1 in the presence of genital coinfections. Although LCs are a target for HIV-1 infection in genital tissues, we found that immature LCs did not efficiently mediate HIV-1 transmission in an ex vivo human skin explant model. However, the inflammatory stimuli TNF-alpha and Pam3CysSerLys4 (Pam3CSK4), the ligand for the TLR1/TLR2 heterodimer, strongly increased HIV-1 transmission by LCs through distinct mechanisms. TNF-alpha enhanced transmission by increasing HIV-1 replication in LCs, whereas Pam3CSK4 acted by increasing LC capture of HIV-1 and subsequent trans-infection of T cells. Genital infections such as Candida albicans and Neisseria gonorrhea not only triggered TLRs but also induced TNF-alpha production in vaginal and skin explants. Thus, during coinfection, LCs could be directly activated by pathogenic structures and indirectly activated by inflammatory factors, thereby increasing the risk of acquiring HIV-1. Our data demonstrate a decisive role for LCs in HIV-1 transmission during genital coinfections and suggest antiinflammatory therapies as potential strategies to prevent HIV-1 transmission.
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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.