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HIV-1 treatment timing shapes the human intestinal memory B-cell repertoire to commensal bacteria

Author

Listed:
  • Cyril Planchais

    (Humoral Immunology Unit, Institut Pasteur, Université Paris Cité, INSERM U1222)

  • Luis M. Molinos-Albert

    (Humoral Immunology Unit, Institut Pasteur, Université Paris Cité, INSERM U1222
    ISGlobal, Hospital Clínic-Universitat de Barcelona)

  • Pierre Rosenbaum

    (Humoral Immunology Unit, Institut Pasteur, Université Paris Cité, INSERM U1222)

  • Thierry Hieu

    (Humoral Immunology Unit, Institut Pasteur, Université Paris Cité, INSERM U1222)

  • Alexia Kanyavuz

    (Centre de Recherche des Cordeliers, INSERM, Sorbonne Université, Université de Paris)

  • Dominique Clermont

    (Collection of the Institut Pasteur, Institut Pasteur, Université Paris Cité)

  • Thierry Prazuck

    (Service des Maladies Infectieuses et Tropicales, CHR d’Orléans-La Source)

  • Laurent Lefrou

    (Service d’Hépato-Gastro-Entérologie, CHR d’Orléans-La Source)

  • Jordan D. Dimitrov

    (Centre de Recherche des Cordeliers, INSERM, Sorbonne Université, Université de Paris)

  • Sophie Hüe

    (INSERM U955—Équipe 16, Université Paris-Est Créteil, Faculté de Médecine)

  • Laurent Hocqueloux

    (Service des Maladies Infectieuses et Tropicales, CHR d’Orléans-La Source)

  • Hugo Mouquet

    (Humoral Immunology Unit, Institut Pasteur, Université Paris Cité, INSERM U1222)

Abstract

HIV-1 infection causes severe alterations of gut mucosa, microbiota and immune system, which can be curbed by early antiretroviral therapy. Here, we investigate how treatment timing affects intestinal memory B-cell and plasmablast repertoires of HIV-1-infected humans. We show that only class-switched memory B cells markedly differ between subjects treated during the acute and chronic phases of infection. Intestinal memory B-cell monoclonal antibodies show more prevalent polyreactive and commensal bacteria-reactive clones in late- compared to early-treated individuals. Mirroring this, serum IgA polyreactivity and commensal-reactivity are strongly increased in late-treated individuals and correlate with intestinal permeability and systemic inflammatory markers. Polyreactive blood IgA memory B cells, many of which egressed from the gut, are also substantially enriched in late-treated individuals. Our data establish gut and systemic B-cell polyreactivity to commensal bacteria as hallmarks of chronic HIV-1 infection and suggest that initiating treatment early may limit intestinal B-cell abnormalities compromising HIV-1 humoral response.

Suggested Citation

  • Cyril Planchais & Luis M. Molinos-Albert & Pierre Rosenbaum & Thierry Hieu & Alexia Kanyavuz & Dominique Clermont & Thierry Prazuck & Laurent Lefrou & Jordan D. Dimitrov & Sophie Hüe & Laurent Hocquel, 2023. "HIV-1 treatment timing shapes the human intestinal memory B-cell repertoire to commensal bacteria," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-42027-6
    DOI: 10.1038/s41467-023-42027-6
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    1. Johannes F. Scheid & Hugo Mouquet & Niklas Feldhahn & Michael S. Seaman & Klara Velinzon & John Pietzsch & Rene G. Ott & Robert M. Anthony & Henry Zebroski & Arlene Hurley & Adhuna Phogat & Bimal Chak, 2009. "Broad diversity of neutralizing antibodies isolated from memory B cells in HIV-infected individuals," Nature, Nature, vol. 458(7238), pages 636-640, April.
    2. Kathrin Moor & Médéric Diard & Mikael E. Sellin & Boas Felmy & Sandra Y. Wotzka & Albulena Toska & Erik Bakkeren & Markus Arnoldini & Florence Bansept & Alma Dal Co & Tom Völler & Andrea Minola & Blan, 2017. "High-avidity IgA protects the intestine by enchaining growing bacteria," Nature, Nature, vol. 544(7651), pages 498-502, April.
    3. Hai Li & Julien P. Limenitakis & Victor Greiff & Bahtiyar Yilmaz & Olivier Schären & Camilla Urbaniak & Mirjam Zünd & Melissa A. E. Lawson & Ian D. Young & Sandra Rupp & Mathias Heikenwälder & Kathy D, 2020. "Mucosal or systemic microbiota exposures shape the B cell repertoire," Nature, Nature, vol. 584(7820), pages 274-278, August.
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