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Schistosoma mansoni treatment reduces HIV entry into cervical CD4+ T cells and induces IFN-I pathways

Author

Listed:
  • Sergey Yegorov

    (University of Toronto
    Suleyman Demirel University)

  • Vineet Joag

    (University of Toronto
    University of Minnesota)

  • Ronald M. Galiwango

    (University of Toronto)

  • Sara V. Good

    (The Hospital for Sick Children, Peter Gilgan Centre for Research and Learning
    University of Manitoba)

  • Juliet Mpendo

    (Uganda Virus Research Institute –International AIDS Vaccine Initiative HIV Vaccine Program)

  • Egbert Tannich

    (Bernhard Nocht Institute for Tropical Medicine, National Reference Centre for Tropical Pathogens)

  • Andrea K. Boggild

    (Department of Medicine, University Health Network
    Public Health Ontario Laboratories)

  • Noah Kiwanuka

    (Uganda Virus Research Institute –International AIDS Vaccine Initiative HIV Vaccine Program
    Makerere University)

  • Bernard S. Bagaya

    (Uganda Virus Research Institute –International AIDS Vaccine Initiative HIV Vaccine Program
    Makerere University)

  • Rupert Kaul

    (University of Toronto
    Department of Medicine, University Health Network)

Abstract

Schistosoma mansoni (Sm) infection has been linked with an increased risk of HIV acquisition in women. Therefore, defining the mechanism(s) by which Sm alters HIV susceptibility might lead to new HIV prevention strategies. Here, we analyze the impact of standard Sm therapy in HIV-uninfected Sm+ Ugandan adult women on genital HIV susceptibility and mucosal and systemic immunology. Schistosomiasis treatment induces a profound reduction of HIV entry into cervical and blood CD4+ T cells that is sustained for up to two months, despite transient systemic and mucosal immune activation and elevated genital IL-1α levels. Genital IFN-α2a levels are also elevated post-treatment, and IFN-α2a blocks HIV entry into primary CD4+ T cells ex vivo. Transcriptomic analysis of blood mononuclear cells post-Sm treatment shows IFN-I pathway up-regulation and partial reversal of Sm-dysregulated interferon signaling. These findings indicate that Sm therapy may reduce HIV susceptibility for women with Sm infection, potentially through de-repression of IFN-I pathways.

Suggested Citation

  • Sergey Yegorov & Vineet Joag & Ronald M. Galiwango & Sara V. Good & Juliet Mpendo & Egbert Tannich & Andrea K. Boggild & Noah Kiwanuka & Bernard S. Bagaya & Rupert Kaul, 2019. "Schistosoma mansoni treatment reduces HIV entry into cervical CD4+ T cells and induces IFN-I pathways," Nature Communications, Nature, vol. 10(1), pages 1-12, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-09900-9
    DOI: 10.1038/s41467-019-09900-9
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    Cited by:

    1. Ludoviko Zirimenya & Fatima Mahmud-Ajeigbe & Ruth McQuillan & You Li, 2020. "A systematic review and meta-analysis to assess the association between urogenital schistosomiasis and HIV/AIDS infection," PLOS Neglected Tropical Diseases, Public Library of Science, vol. 14(6), pages 1-13, June.
    2. Valentina Z. Petukhova & Sammy Y. Aboagye & Matteo Ardini & Rachel P. Lullo & Francesca Fata & Margaret E. Byrne & Federica Gabriele & Lucy M. Martin & Luke N. M. Harding & Vamshikrishna Gone & Bikash, 2023. "Non-covalent inhibitors of thioredoxin glutathione reductase with schistosomicidal activity in vivo," Nature Communications, Nature, vol. 14(1), pages 1-19, December.

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