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

Cyril Planchais, Luis M. Molinos-Albert, Pierre Rosenbaum, Thierry Hieu, Alexia Kanyavuz, Dominique Clermont, Thierry Prazuck, Laurent Lefrou, Jordan D. Dimitrov, Sophie Hüe, Laurent Hocqueloux and Hugo Mouquet ()
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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
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

Nature Communications, 2023, vol. 14, issue 1, 1-17

Abstract: 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.

Date: 2023
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DOI: 10.1038/s41467-023-42027-6

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