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

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

Edité par CCSD ; Nature Publishing Group -

International audience. 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.

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