Exposure to Secreted Bacterial Factors Promotes HIV-1 Replication in CD4 + T Cells - Institut Pasteur Access content directly
Journal Articles Microbiology Spectrum Year : 2023

Exposure to Secreted Bacterial Factors Promotes HIV-1 Replication in CD4 + T Cells

Abstract

Microbial translocation is associated with systemic immune activation in HIV-1 disease. Circulating T cells can encounter microbial products in the bloodstream and lymph nodes, where viral replication takes place. The mechanisms by which bacteria contribute to HIV-associated pathogenesis are not completely deciphered. Here, we examined how bacteria may impact T cell function and viral replication. We established cocultures between a panel of live bacteria and uninfected or HIV-1-infected activated peripheral blood CD4-positive (CD4+) T cells. We show that some bacteria, such as Escherichia coli and Acinetobacter baumannii, sustain lymphocyte activation and enhance HIV-1 replication. Bacteria secrete soluble factors that upregulate CD25 and ICAM-1 cell surface levels and activate NF-κB nuclear translocation. Our data also demonstrate that CD25 polarizes at the virological synapse, suggesting a previously unappreciated role of CD25 during viral replication. These findings highlight how interactions between bacterial factors and T cells may promote T cell activation and HIV-1 replication. IMPORTANCE People living with HIV suffer from chronic immune activation despite effective antiretroviral therapy. Early after infection, HIV-1 actively replicates in the gut, causing the breakage of the intestinal epithelial barrier and microbial translocation. Microbial translocation and chronic immune activation have been proven linked; however, gaps in our knowledge on how bacteria contribute to the development of HIV-related diseases remain. Whether T cells in the peripheral blood react to bacterial products and how this affects viral replication are unknown. We show that some bacteria enriched in people living with HIV activate T cells and favor HIV-1's spread. Bacteria release soluble factors that cause the overexpression of cellular molecules related to their activation state. T cells overexpressing these molecules also replicate HIV-1 more efficiently. These results help us learn more about how HIV-1, T cells, and bacteria interact with each other, as well as the mechanisms behind chronic immune activation.
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pasteur-04082639 , version 1 (26-04-2023)

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M. Znaidia, Y. de Souza-Angelo, S. Létoffé, I. Staropoli, L. Grzelak, et al.. Exposure to Secreted Bacterial Factors Promotes HIV-1 Replication in CD4 + T Cells. Microbiology Spectrum, 2023, 11 (2), pp.e0431322. ⟨10.1128/spectrum.04313-22⟩. ⟨pasteur-04082639⟩
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