%0 Journal Article %T Exposure to Secreted Bacterial Factors Promotes HIV-1 Replication in CD4 + T Cells %+ Virus et Immunité - Virus and immunity (CNRS-UMR3569) %+ Génétique des Biofilms - Genetics of Biofilms %+ Vaccine Research Institute [Créteil, France] (VRI) %A Znaidia, M. %A de Souza-Angelo, Y. %A Létoffé, S. %A Staropoli, I. %A Grzelak, L. %A Ghigo, J. %A Schwartz, O. %A Casartelli, N. %Z Work in the O.S. laboratory is supported by Institut Pasteur; Urgence COVID-19 Fundraising Campaign of Institut Pasteur; Fondation pour la Recherche Médicale (FRM); ANRS; the Vaccine Research Institute (ANR-10-LABX-77); Labex IBEID (ANR-10-LABX-62-IBEID); ANR/FRM Flash Covid PROTEO-SARS-CoV-2; ANR Coronamito; IDISCOVR; the INCEPTION program (Investissements d’Avenir grant ANR-16-CONV-0005); the French Government’s Investissement d’Avenir program, Laboratoire d’Excellence, Integrative Biology of Emerging Infectious Diseases (grant no. ANR-10-LABX-62-IBEID); HERA European funding; and the NIH PICREID (grant no. U01AI151758). M.Z. is supported by the ANRS. Y.d.S.-A. is supported by Calmette & Yersin funding (Y-SU11007 [PA/MLH/N 70/12]). J.M.G. and S.L. were supported by a grant from the French government’s Investissement d’Avenir Program, Laboratoire d’Excellence, Integrative Biology of Emerging Infectious Diseases (grant ANR-10-LABX-62-IBEID) and the Fondation pour la Recherche Médicale (grant DEQ20180339185). %< avec comité de lecture %@ 2165-0497 %J Microbiology Spectrum %I American Society for Microbiology %V 11 %N 2 %P e0431322 %8 2023-04-13 %D 2023 %R 10.1128/spectrum.04313-22 %M 36853052 %K Gram-negative bacteria %K Gram-positive bacteria %K HIV-1 %K T cells %Z Life Sciences [q-bio]Journal articles %X 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. %G English %Z We thank J. Dufloo, F. Mammano, and F. Roesch for critical readings and editing of the manuscript. We thank members of the Virus and Immunity Unit, especially T. Bruel and N. Saunders, for helpful discussions and assistance. We thank the Imagopole (Institut Pasteur) and the IAH (Image Analysis Hub) for help in image acquisition and analysis. We especially thank J. Elis for his continuous support %2 https://pasteur.hal.science/pasteur-04082639/document %2 https://pasteur.hal.science/pasteur-04082639/file/spectrum.04313-22.pdf %L pasteur-04082639 %U https://pasteur.hal.science/pasteur-04082639 %~ PASTEUR %~ CNRS %~ UPEC %~ UNIV-PARIS %~ UNIVERSITE-PARIS %~ ANR %~ FRM %~ VIR-IMMUN %~ PASTEUR_UMR3569